most fluid are intracellularisoosmotic conc.

Na+/K+ ATPase depends on:-Na conc inside-K+ outside-Energy supply(ATP)-Temprature-Inhibitors? Ouabain

RM potential-70mV for majority of neurons

Threshold potential-55mV

Equilibrium potentialhypothetical potential difference across cell membrane at which net cross of ions due to gradients would be equal to 0

Sensory neuron-graded potentials-myelinated/unmyelinated axons

Chapter 8 - APs, GPs etc.

Axon - transmits electrical impulse to distal end where electrical signal -> chemical via:Neirotransmitter, neuromodulator,(neurohormone)-Axons lack RER and ribosomes hence all proteins are synthesized in soma for axonal transportSlow and fast axonal transport

Glial cells - support for neuronsPNS: Schwann cells - myelination (1 node 1 Sch cell)Satellite cells - ganglions CNS:Oligodendrocytes - myelination (several nodes)Microglial cells - immune responseAstrocytes - blood brain barrierEpendymocytes - neura stem cells + compartments

Nerve and muscle cells are excitable tissuesVm - resting membrane potential-Uneven distribution of ions across the membrane-Mainly due to K+-90mV or - 70mV in resting neuronNa+ in depolarize - too much K+ out hyperpolarize(become more negative)Hypopolarize(become more +/ närmare 0 / more excitable)

1. Mechanically gated ion channels -In sensory neurons open to physical forces like pressure or stretch2.Chemically gated ion channelsRespond to ligands(neurotransmitters/neuromodulators) & intracellular signal molecules.3.Voltage gates ion channels-Resoond to change in resting membrane potential - depends on threshold—>Depolarization opens fast gated Na+ channels and then K+ channelsThis can work as a swing door - swings back closed when electrical signal passedIt can also be inactivated - works like an automatic timed door (off button)

Net flow of ions depend on electrochemical gradient Graded potentials -Variable in strength-Loose strength on the way (stone in water)-If the stone is big then more likely to fire AP-> amplitude is directly proportional to strength of triggering event-Occurs in cells body(soma)-Loose strength due to K+leak and cytoplasmic resistanceAction potential-Large depolarizations-Do not loose strength -Rapid signalling over long distances -Works like a domino-Peaks at + 30mV-Equilibrium for Na+ at +60mv?-Falling phase: increase of K+ leak - inc negativity and fall of AP-SPeed depends on diameter and ions leakage - large and myelinated -> fastest conduction

Graded Potential Action potential

Input signal Conducting signal

In cell body trigger zone->axon

MechanicalChemical or voltage G

voltage gated

Na+ K+ Cl- ions Na+ and K+

DepolarizingHyperpolarizing

Depolarizing

Summation All or none

Gated channelsNO threshold

threshold -> open ion chan

no minimumfor initiation

threshold -55mV needed

no refractory period refractory period

strength by frequency No AP in refractiory period

Na+ channels has two gatesActivation gate and deactivation gate-55mV - Activation gate opens0mV - Na+ enters+30mV - inactivation gate closes (peak of curve)Repolarization - activation gate closes and inactivation gate open - reset to original state

Absolute refractory periodNa+ channels must reset to original position (1-2 millisek)-> AP cannot fire now and no moving backward

The relative refractory period - Larger than normal stimulus can trigger AP

At depolarization site of axon + inside -outsideNomal: - inside ++outside

Nodes of ranvier has high concentration of Na+ channels-> Saltatory conduction, like jumpingIn demyelinating diseases like MS - conduction is slowed

Chemical factors-Neurotoxins blocking Na+ channels, neurotoxins fails to pass signal to postsynaptic neuron-Botulin?-Snake poison?

Normal K+ conc = 3.5-5mmol/LHypokalemia-Increased electronegativity-Farther away from threshold-Presents as muscle weakness

Hyperkalemia-Decreased electronegativity (more + cell) - K+ will not leak out as fast(osmos)-Hypersensitive neurons-Fire AP to smaller GP

Hypernatremia - hypersensitive neuronsHyponatremia - muscle cramps

Electrical synapses-Mainly in CNS-Smooth m.-Gapjunctions allow chemical signaling molecules to pass electrically

Chemical synapses-Electrical signal becomes a chemical neurocrine-Neurotransmitter - rapid and local in one synapse-Neuromodulator - can be synaptic and non synaptic, slower acting. Auto/paracrine

Neurohormones bind to ionotropic receptors or metabotropic(G-protein coupled)Circulate in blood

NeurotransmittersReleased from vesicles on demand by exocyotosis into synaptic cleftBotulin and other toxins block this exocytosis apparatus

Glutamate - main excitatory in CNS, act on ionotropic and metabotropic receptors. aspartate is another one excitatoryGABA - Main inhibitory in brain made from glycineGlycine - main inhibitory in spinal cord - Cl- channels for hyperpolarizationSupstance P - pain pathways and pain relier(opiods)ATP/AMP - Can act as Nts, purines. In CNS and heartNitric Oxide -Acetylcholine-Epinephrine-Norepinephrine-

Depolarization leads to Ca2+ influx along gradient -> binds to proteins triggering exocytosis-> Nt released into synaptic cleftThen vesicles are endocytosed and retrogaededly transported back.

AcH becomes Acetyl + choline by Acetylcholine esteraseMAO breaks down norepi in mitochondria

-Ability for neurons to change activity at synapses - synaptic plasticity

2nd msg metabotrppic by neuromodulatorsFast ion channels by neurotransmitters

Cell response of postsynaptic neuron determined by summed input from presynaptic neuronEPSP - excitatory depolarization Na+ or Ca2+ inflowIPSP - inhibitory hyperpolarization - Cl- inflow or K+ outflowSuprathreshold - EPSP> IPSP -> AP

At postsynaptic cellSpatial summation: graded potentials arrive at different regions, summedE.g inhibition - 3x convergence: 2x EPSP + 1x IPSP -> subthreshold sum! Inhibition does not always require multiple neurons - if IPSP/EPSP arrive close in time they can be summed

Temporal summation - GPs close in timeSpatial + temporal summation = postsynaptic integration

Presynaptic inhibition-Inhibitory neursons decrease amount of neurotransmitter release(depolarization)-hyperpolarizationMore precise than postsynaptic inhibition-> Target response changeThis is all done by neuromodulators -> no response or weaker response in target cell A

Upon injury to a neuron-proximal stump regenerates by support of glial cells-distal stump macrophaged

Factors effecting nerve conduction-pressure - tingling, CP ulnar nerve-decreased temp -> reduced pain. if ice crystals in cell, irreversible-toxins-etherethyl ethanol - destroy lipid bilayer, on lab, irreversible

Chapter 6 - CommunicationLocal communicationGap junctions-Cytoplasmic bridges between adjacent cells-2x connexins -> connexons(protein channel) that opens/closes-For small ions and molecules:ATP amino acids-The only mean by which electrical signals pass directly from cell->cell

Contact dependent signalsSurface molecule of one cell ->membrane protein of another cellIn nerve development and immune systemParacrine: Cells in vicinity. Histamine acts this wayAutocrine - cell act upon self

Long distance - Endocrine systemChemical - hormones in bloodIn contact with all cells - the ones with correct receptors mediate a response

CytokinesLocal and long distanceSynthesized in response to stimuliAct broader than hormones, produced by all cells, made on demand

A cell can respond to the signal if it has appropriate receptorLigand->receptor->activation->intracellular activation->synthesis of target proteins->response

RECEPTORSLipophilic - signalling molecules can diffuse through membrane and bind to nucleus/cytosol membrane. Common in gene activation. Usually hormones

Lipophobic - Ligand need receptor protein in membrane. -> Rapid response-Ligand gated channel-Gprotein coupled receptor - a transducer - activates 2nd msg system-Receptor enzyme-Intergrins

G-protein coupled receptors-Pass 7x across membrane-Inactive G-protein bound to GDP-GDP->GTP activates Gprotein ligand binds->phospohorylating->activation-Amplifyers: adenyl cyclase and phospholipase C

Lipophobic G-protein - cAMPAdenyl cyclase converts ATP-> cAMPcAMP activates protein kinase A - PKA->phosphorylation and signal cascade

Lipid derived G-protein - phospholipase CPhospholipase c converts a membrane phospholipid intoDiaglycerol - activates PKCIP3 - Leaves membrane, RyR Ca2+ channel on ER -> C2+ release in cytosol

IntegrinsAnchored to cytoskeletonImportant in blood clotting

Ligand gated channelsFastestIon channels along gradients

Orphan receptors - no known ligand- Eicasoid signal molecules from archidonic acidLeukotriennes??

SIGNALING MOLECULES/LIGANDSCalcium-Voltage/Ligand/Mechanically gated Ca2+ channels-Released intracellularly by IP3-Stored in ER-Ca2+ to calmodulin - enzyme activity in smooth m.-Ca2+ to troponin -> m. contraction-Ca2+ to channels altering their state (Ca2+ activated K+ channel)

NO - dilates bloodvessels. cGMP formation. Neurotransmitter in brainCO-toxicH2S - relaxes bloodvessels in cardiovascular system

Usually cell response depends on receptor not on ligandLigand -> response A in tissue Xresponse B in tissue YThis is explained by ligands binding to different isoforms - e.g adenergic receptors.Epinephrine to alpha receptors - vessel constriction Epinephrine to Beta receptors - vessel dilation

Also different ligand can bind to same receptornorepi/epi in fight/flight respond can bind to both alpha and beta receptors

Antagonist - ligand that occupy/blockAgonist - ligand that activate

Down regulation - decrease in receptor on surface by endocytosis. Too much agonists e.g. Can also be done by desensitization (phosphorylation of B receptor)Drug tolerance can partly be explained by down regulation - not as effective response to high ligand concentration. Up regulation - Less internalization, hypersensitive receptors. Response to too low ligand concentration

Homeostatic reflex pathways-Some systems are under tonic control - signal always present, volume up/down-Systems not under tonic control are under antagonistic control - e.g autonomic control of HR-Chemical signals having opposing effects - antagonistic-An antagonistic signal in one tissue may be cooperative in other

Sphincters are under tonic controlOther smooth m.-undre antagonistic control

Reflex control pathwayStimilus->sensor/receptor->input signal -> integrating center -> output signal ->target -> response

Stimilus - change of variable (02, BP)->sensor/receptor - constantly monitors environment of variable->input signal - sensor sensed change, sends a signal to reflex integrating center-> integrating center - compares input with set point-> output signal - initiated if variable changed out of range. sends efferent chemical/elecrtical signal to->target - effector cell that carries out appropriate-> response

! Sensory receptors respond to changes in environment not the same as protein receptorsCentral receptors - brain, eye, ear , nosePeripheral receptors - in skin, internal organs etcAll sensors has a threshold, if stimuli is below - no response

Integrating center in endocrine reflexes - the endocrine cell itselfIn CNS - brain and spinal cord

If there is a single stimulus IC has a simple taskUsually multiple - IC sorts out what is most important’Output is always electrical and chemical by efferent neuron in neural reflexesSecreted in blood by endocrine R

The cellular response might be different from systemic response to reflexE.g vasodilation of cells causes systemic response of increased bloodflow

Neural reflex Endocrine reflex

Specifity 1x neuron specific target Lot of exposed cells,need specific receptor

Nature elecrical & chemical chemical into blood

Speed rapid slower

Duration of AP short can be longer with neuromodulators

longer response

Coding for identical signalintensity:frequency of signal

intensity:amount of hormonesecretes

These 2 reflex systems better viewed as a combo not two separate systemsComplex reflex control centers has more than one integrating center

Simple endocrine pathwayEndocrine cell is both censor and IC ->hormone releaseNo input needed-Target is any cell with appropriate receptor E.g insulin secretion

SImple neuronal reflex - knee jerk

Neurohormone reflex - identical to neural except neurohormone travel in bloodE.g breastmilk - oxytocin reflex

Autonomic nervous system

PNS efferent divisionSomatic motor neurons - skeletal m. controlAutonomic neurons - smooth m., cardiac m., glands, adipose tissue

Autonomic division-involuntary and self governing-two efferent neurons CNS->GGL GGL->TISSUE-Divergence! 1 preggl neuron synapse with 8-9 post-> 1 CNS signal effect a lot of target cells simultaneously-Cell bodies in lateral horn on spinal cord

Peripheral ganglions has neurons as small integrated centerstechnically a reflex could be integrated here

Antagonistic control - hallmark for ANS! Exceptions are sweat glands, smooth m. of blood vessels and sphincters - sympathetic tonic control

Sympathetic division - fight/flight-T1-L2-Sphlancninc nn.-Use acetylchole(nicotinic) pre & norepinephrine(adenergic) post-Paravertebral ggl in sympathetic trunk-Pre vertebral ggl - celial, SMA/IMA -terminal ggl. - urinary bladdr & rectum- ! sweat glands use Ach-Ach(muscarinic)-adrenal medulla is a form of ganglion, no postsynaptic fibers. Only Ach nicotinic. Secrete epi/norepi -> bloodChromaffin cells-inc HR, CO, dilating bronchioles-blood from GI tract -> skeletal m.-pupil dilaiton

Parasympathetic divison - rest and digest-CN III, VII, IX, X - 37910-Ganglions near or within organs-Sacral outflow(pelvic sphlancnic) S2-S4-pupil constriction-accomodation for near vision-bronchial diamete inc. resistance-inc peristalsis-erection-use acetylcholine on nicotinic and muscarinic

Feature Cholinergic Nicotinic

Cholinergic muscarinic

Adenergic Alpha1

Adenergic Alpha2

Adenergic B1

Adenergic B2 Adenergic B3

Info Autonomic Nn/N1

Skeletal m. Nm/N2Only presynaptic

Autonomic ggl M1>Ca2+ release

Myocardium M2coupled K+ ch

Smooth m./gland M3

Sweatglands

Can be presynaptic at autocrine cells

Postsynaptic at target cells

in eye(dilator p)in fingers etc for constric

presynaptic at target cell

decreaserelease of norepi onsympatheticnerves

in eye(dilator p)

renin release

not innervated

present in A-venuleshunts -dilate

fat

StructurePrefer:

IonchannelsIonotropic

7 subunitMetabotropic

MetabotropicNorepi/epi

MetapotropicNorepi/epi

Norepi/epiequally

Norepi/epi Norepi/epi

ANS part Sympathetic/Parasympathetic+skeletal m.

Parasympathetic Sympathetic Sympathetic Sympathetic

Sympathetic Sympathetic

G type G-protein phospholipase C

G-protein phospholipase C

Agonist AchSmall dose of nicotine

AcetylcholineMuscarinepiloarpine

Norepiphenazoline

formoterolsalbutamol

Antagonist Large dose of nicotineBotulin

Atropine Phentolamine Phentolamine PropranololMetroprolol

Propanolol

Blocking-> curariform drugsblock Ach binding

Atropine ->Reduce diarrhea and dysapnea

Blocked in atrial hypertensionPrazosine

Slows HR some vasoconstriction

Stimulation->

Decreased HRPeristalsis etc

Constrict airwayscalm breathing

SphinctingSmooth m. Vasoconstriction GI + limbsIncreased BP

Nässpray stimulatesfor vasoconstriction-> less swelling

GI tract relaxationLess secretiondecrease cAMP

Increase HR-Inc force ofcontraction+ cAMP

++ cAMPvasodilationin bronchiolean skeletal m.

-relax bladderand uterus-decrease GImotility

++ cAMPreleases triglycin up to 70% maxexcercise

Bronchial Asthma

Block by atropine Stimulate withB2 agonist-formosterol

Choose specificIf B1 also blocked heart pounding

Arterial Hypotension

Stimulate for vasoconstriction - norepi

+ give dopamine against decreased bloodfin glomerulus

Stimulatefor incHR andforcenorepi/epi

Ischemic heartdisease

Block for decreased 02 consumption

less force o HR

If B2 also blocked(nonspecific)

difficulty breathing may occur

Intestinal colic

Block by atropinedecrease peristalsis

Fight/flight inc sweatingAcH release

decrease cAMP

dilator pupillae

constriction inlimbs and GI tract

sphincter activation

less saliva inc. HRand force

bronchodilation

vasodilation inskeletal m.

relax smoth m.detrusor m.

shunt activatio

Immodium against diarrhea act as an opioidstimulates K+ outflow -> hyperpolarizing, makes cell less prone to fire - less Ach releasedinhibits adenyl cyclase - less camp - less Ach released

Decrease of cAMP promotes secretionAll B-recetptors increase cAMP

Increased cAMP will promote relaxation in smooth muscle, while promoting increased contractility and pulse rate in cardiac muscle.

Junction between postganglionic autonomic neuron and effector(target) cell - neuroeffector junctionA single postganglionic neuron can affect a large area of target tissue

-Autonomic neurotransmitters are synthesized in the axon or body-More NT -> larger and stronger response-Enters by diffusion or metabolized in ECF & transported to other cells-Eg norepinephrine metabolized by MAO or repacked into vesicles

Cocaine - an indirect agonist that blocks reuptake of norepi inte adenergic terminals -> prolonged excitatory effectAmphetamine - increase NE activityAnticholine esterase - block choline esterase (Ach degradation)

Aterial hypotension - dopamine D1 agonist -> renal vasodinaltion

The somatic motor division1x neuronSomatic pathways are always excitatory-Cell bodies in ventral horn of spinal cordNeuromuscular junction - motor end plate AcH nicotinic receptor NAcHr receptorSimilar to simple nicotinic but it binds to a-bungarotoxin too

AP-> Ca2+ channel leak in -> Ach Release into synapse -> NacHr on motor end plate-> gated Na+ channels -> along T-tubules ->depolarization and contraction

Drugs affecting neuromuscular junctionDepolarizing - nicotine, metacholine -> prolonged depolarization -> spasmNon-depolarizing(Curariform drugs) - d-tubocurarine binds to N2 receptor prevent ACh from binding -> no excitation of m. cell possible -> death(suffocation)AcH esterase inhibitors - DFP - decrease AcH inactivation -> inc AcH cell exposure and inc response. Used as a chemical weaponBotulin(Botox) - inhibit ACh release from nerve endings. Management of myasthenia gravis & wrinkles-from clostridium botulinium-destroy SNARE- proteins

Strycknos toxifiera - large plant. Currare block N2 cholinergic receptors -> no muscle depolarizationBlue poison dart frog batrachotoxin -> irreversible opening of Na+ channels -> unceasing depolarization -> death

Myasthenia gravisDisease in loss of Ach receptors on skeletal m. Autoimmune. No depolarization -> no contraction

At rest axon terminal of motor nerve relases mini amount of AcH - miniature end plate potentials-Directly proportional to Ca2+-Inversely proportional to Mg2+

MUSCLES CHAPTER 12-13skeletal m. - striated, multinucleated.Stapedius m. smalles striated in bodygluteus maximus - most massivelatissimus dorsi - widestsartorius - longest-cells electrically isolated-hormone insensitive-40% body mass

cardiac m.single nucleusstriation, involuntary, intercalated discgapjuncitons

smooth m.single nucleus, non striated, involuntary, gapjuncitons-hormone sensitive

Contractility - ability to shorten with generation of forceExtensibility - stretching beyond normal lengthElasticity - ability to return to original resting length after stretch

Skeletal m.-Cannot contract without somatic motor neuron-their contraction is not directly influenced by hormones-flexors/extensors are antagonistic muscle groups

SarcoplasmSarcolemmaMyofibrils - one muscle fibers is like 100 myofibrilsSarcoplasmic retuculum SR - around each myofibrilT-tubules - allow AP to flow from surface to interior rapidly

Myosinhas light chains and heavy chains- motor domain and actin binding site—> Thick filaments

ActinG-actin to F-actineach G-actin has a myosin binding site—> Thin filaments

SarcomereZ-ZThin filaments attach to Z-discThick filaments to M-line

Muscle contraction-Force created by contraction - tension-Shrinks sarcomereContraction is the active creation of tensionLoad opposes contractionRelaxation is the release of tension

Titin - stabilizes myosin (TM)Nebulin - helps alligh actin (elli gick NA) - promotes strong acting-myosin interactions

Actin-myosin sliding-I band and H zone disappears shortening muscle-Myosin pulls on actin like a rope hailing - power strokes -Myosin ATPase provide energyCa2+ increases -> Ca bind to troponin-> troponin binds to tropomyosin that blocked actin binding sites on G-actin-> myosin can bind->power stroke

Relaxed state just before power stroke - 90 degree cross bridge

The rigor state - 45 degree cross bridge relative to filamentNo metabolism- no ATP-> muscles do not bind ATP -> rigor mortisthe tightly bound state

AcH released into synapse -> opening Na+ influx, K+ out -> end plate potential - Always above thresholdAP is conducted along T-tubules opening Na+ channelsAP in T-tubules alters DHP receptorDHPs open RyR Ca2+ release channels from SR->Ca2+ release from SRCa2+ binds to troponin allowing actin-myosin binding

DHP-RyR - electrochemical coupling. No extracellular Ca2+ needed

Note!In response to depolarization of T-tubule change of shape of DHPR is necessary for RyR activationwhile influx of Ca2+ is not

RelaxationCa2+ ATPase pumps Ca2+ back into lumen

one contraction-relaxation cycle - a twitchlatent period - between AP and muscle tension. Time for Ca2+ release and troponin binding

-Resting muscle stores ATP in phosphocreatine binds -fast intensive-=2 dependent fatty acid - used in light exercise-O2 dependent glycolytic - heavy exercise

Fatigue depends on not fast enough Ach synthesis and K+ release, an imbalance in membrane potential.

ATP needed for-Na+/K+ ATPase-Contraction (power stroke)-relaxation - active pumping of Ca2+ back to SR

Treppe effect-Graded response-In muscle rested for a prolonged period-Each contraction is stronger than previous until equal after a few stimuli

Slow twitch fibers -myoglobin rich red m. fiber.better blood supplyOxidative.Fatigue resistant.Smaller diameterFast twitch FOG IIA -large diameter- glycolytic rapid ATP split - contain myosin- white fibers, fewer and smaller mitochondriaFast twitch FG IIB - Pump Ca2+ faster. Fatigue most easily

Oxygen concentration is a factor - depend on myolglobin (has high O2 affinity)

FatiguePsychological - emotional stateMuscular - ATP depletionSynaptic - neuromuscular junction, lack of AcH

The tension a muscle can generate is directly proportional to number off cross bridges between thin and thick filaments - why optimal sarcomere length exists! Single twitch tension is determined by sarcomere lengthThen force generated by contraction can increase by increasing frequency at which APs stimulate muscle fibers

No time to relax completely -> summationUnfused tetanus - m. fibers partially relax - some Ca2+ can be recycled between contraction complete tetanus - no relaxation, flat line

Allo or none law for muscle fibers-Contraction of equal force in response to each individual AP when they arrive at sufficiently long intervalsGraded for whole musclesForce of contraction of whole muscle range from weak -> strong depending on stimulus strength.

Motor unit Somatic motor neuron + fibers it innervates(one fiber type only)more fine MU for e.g eye, bigger for like thighThere are fast twitch MU and slow twitch MU-Each alpha motor neuron innervates a motor unit-all cells in an MU contract simultaneously-small MU are recruited first(low threshold, size principle)

Graded force/contraction depending on-Changing types of active MU-And changing number of MU responding at any given timeDone by recruitmentWe are able to maintain constant tension due to variations in MU. The fatigued ones overlapped by pigga

->summation of force= function of stimulation rate

FINAL COMMON PATHWAY:Alpha motor neurons collecting inputs -> neuromusclular junction convergence of many neurons onto a single motor neuron

IsoTONIC contraction - creates force and moves loadSarcomeres shorten more but elastic elements are already stretched -> shortening of the muscle = concentricEccentric - tension maintained but muscle lengthens

Isometric contraction - force without moving load - staticCreates force but do not shorten, elastic elements.Sarcomeres still shorten(contract) but the elastic elements streches to maintain constant length-> Firm and ready for action at all times ->postural muscles of body

ATP for muscle contractionCreatine phosphate 3-15sekAnaerobic respiration 10sek-2min- glc -> ATP + lactic acidAerobic respiration - 38ATP/1 glc

Gravity produces tonic muscle tension

Smooth m.phasic- usually relaxedtonic - maintaining some level of tension - e.g sphincters

single unit smooth m. - linked by gap junctions -multi unit - cells not electrically linked, act independently - like iris/ ciliary m.

most smooth m. are single unit - visceral-actin myosin interaction-contracts by increase Ca2+ levels in cytosol-smooth m. relax and contract more slowly -require less ATP to generate and maintain force-no fatigue-no sarcomeres-single nucleated-higher sensitivity to ion conc. changes -tends to contract in response to sudden stretch(myogenic autoregulation of bloodflow)-amplutude of contraction constant - muscle length varies

Myosin phosphorylation controls contractionCa2+ binds to calmodulin-> phosphorylation of myosin light chain(kinase)Myosin ATPase -> contractionMLCP control Ca2+ sensitivityDense bodies

Autonomic control-Antagonistic control by sympathetic/parasympathetic-Bloodvessels(symp) and sphincters under tonic control-Linked to G-protein coupled receptors-Phospholipase C-> DAG relase of Ca2+ -> increase of MLCK and MLCP -> contraction-adenyl cyclase-> increase of cAMP -> increase of myosin phosphatase activity -> relaxation

Control of body movement and reflexessomatic reflexes - somatic motor neuronsautonomic reflexes - autonomic neuronsspinal reflexes - integrated in spinal cordcranial reflexes

Primitive reflexes/newbron - originate in brainstem, disappear in normal brain development. CP kids may retain theseInnate reflexes - born with it, may disappearLearned reflexesMonosynaptic reflex - A sensory afferent synapse direcly on a motor neuron. Only somatic motor reflexesPolysynaptic - at leas one interneuron, all autonomic reflexes, 1x afferent, 2x efferentSuperficial reflexes - stimuli of mucus/skin - corneal, cremasteric, suckling, plantarDeep reflexes - stretch reflexesSegmental - stretch reflexIntersegmental - flexion withdrawal - polysynaptic reflexessuprasegmental - swallowing

Most reflexes does not need to involve brain but brain can:Inhibit by increasing electronegativity (hyper polarize)Facilitate by decreasing electronegativity (depolarize)

The reflex arc - basic functional unit of our ns.

Autonomic reflexes-Visceral-Polysynaptic-could be spinal BUT modulated by excitatory/inhibitory signals from brain, like urination-Higher control of a spinal reflex - a learned response(?)-tonic activity

Skeletal m. reflexesMuscle info -> CNS -> Response:Contraction leas to activation of somatic motor neurons ORRelaxation - a result from absence of excitatory input by somatic motor neuron - they are inhibited

Proprioreceptors(sensory) - info of position and effort. Input to CNS via sensory neurons.CNS integrates via excitatory/inhibitory interneurons. Can become perception in cortex. Somatic motor neuron - carry output signal.Neurons innervating skeletal m. - called alpha motor neurons innervates extrafusal motor fibers

The 3 proprioreceptors1. Muscle spindle-stretch receptors -> causes stretch reflex - MYOTATIC REFLEX-paralell to extrafusal muscle fibers-each m. spindle in a capsule enclosing intrafusal m. fibers(lack myofilaments centrally, smaller and parallel to extrafusal fibers and can be stimulated by gamma motor neurons)-Has contractile ends but central region lacks myofibrils-Central region is excitable by 1. stretching of entire m. or 2. stretching of contractile ends(m. length remain constant!)-Innervated by gamma motor neuronsFunciton-reflex for muscle tone-transducers(sensors) of muscle stretch, amplitude and velocity)-indirect not voluntary initiator of m. contraction - patellar reflex

Gamma neuron stimulated ->The noncontrictile part is wrapped in sensory nerve endings -> info into sensory neurons -> spinal cord -> alpha motor neurons innervating that m.! Resting muscle has enough stretch to activate this tonic control -> muscle toneThis is also leads to reflex contraction to precent overstreching = stretch reflex.Stretch reflex maintains muscle tone and posture

! Prescence of gamma motor neurons keeps spindles active no matter length.Muscle contraction by alpha motor neurons while gamma MN keeps spindle tense at contractile end.Muscle spindle reflex: Putting a load in 90degree elbow hand - hand will fall and the set back into normal position due to muscle spindle.

Types of fibers within muscle spindle:

Type Ia - primary afferent fiber excited by both nuclear bag and chain fiber. 17mikrom in diameter-. Dynamic response to stress.short stretch.Excite alpha-mn via Monosynaptic pathwayhighest velocityType II - secondary afferent is only excited by chain fiber (thinner). 7mm.Static response to stress.Sustained stretch.mono and polysynaptic pathway

Both excite alpha motor neurons of that muscle Ia and II afferentes secrete glutamate

during motor activity both alpha and game motor neurons activated -> a-g coactivation

2. Golgi tendonJunction of tendon and muscle fiber-Active during isometric contraction(no load moved, force but do not shorten) hold a glass of water, yoga-Reflex Causes relaxation - prevent överansträngning-Free nerve endings inside CT capsule embedded in collagen fivers-Embedded in collagen fibers

Ib fibers - do not synapse directly on motor neuronsGTO much less sensitive to muscle stretch than stretch repectors - nerve endings are encapsulated

Muscle contraction tightens the fibers, squeezing nerve endings that fire afferents -> spinal cord-> inhibitory interneurons activation-> decreased excitatory output inalpha motor neuron->decreased contraction

This reflex slows muscle contraction an prevents over contraction !! Think back on holding the load in 90 degree angle, if the load becomes heavier then the tension the muscle can develop -> inhibition of alpha motor neurons-> relaxation and the arm falls.Important to protect the muscle fire from damage!

Deep tendon reflex-opposite of stretch reflex-activate GTO -> inhibitory interneuron -> decrease alpha neuron fire-stimulate contraction of antagonistic muscle(active & elasticity) ->contractive m. relaxes

Passive stretch of m.-spindle activated-> contraction of extrafusal m. fibers(stretch reflex)-not stretched enough for GTO

Active contraction- central activation of alpha MN-> contraction of extrafusal m. fibers-muscle spindle relaxed(inactivated)GTO activated - causes relaxation

Active contraction with gamma contraction-intrafusal and extrafusal fibers contract Ia and II afferents-GTO activated but inhibition too weak-when load becomes too great inhibition is strong enough and reverse mitotic reflex starts(muscle relaxation)

3.Movement around joints- diverging and converging pathways - myotatic unit-simplest reflex in myotatic unit - monosynaptic stretch reflex1- sensory neuron from spindle 2. alpha motor neuron to muscle

Knee jerk reflex1.monosynaptic stretch reflex of quadriceps - end of the stretch reflex is monosynaptic2. reciprocal inhibition(polysynaptic) of antagonist (hamstring)

1. Tap-> stretch-> spindle activation-> AP in sensory neuron->synapse in spinal cord-> efferent motor neuron->contraction of quadriceps — monosynaptic2.synapse in spinal cord also activate inhibitory interneuron -> synapse to inhibit motor neuron in hamstring(relaxation) —polysynaptic

Flexion reflexes - limb away from panful stimuli-Polysynaptic-Rely on divergent pathways in spinal cord-Takes longer time than spinal reflex-Both relaxation of antagonist and alpha motor neuron activation -> flexion

Noci(pain) receptor->affferent neuron->spinal cord->divergence:1.excitatory interneurons - alpha MN contraction -> flexion2.inhibitory interneursons to cause relaxation of antagonist

Flexor reflexes especially in e.g legs - accompanied by crossed extensor reflex:-Maintains balance when one foot is off the ground-> extensors contract in supporting leg, relax in flexed legOur natural gaair pattern, crawl, walk, run

MOVEMENT

Reflex movement-Least complex-Primarily spinal cord-Sensory input can reach brain for coordinationPostural reflex-Integrated in brainstem-Input from visual, vestibular and muscular proprioception-Reason for like blind seeing-Sensory feedback is used to refine reflex movement

Voluntary movement-Integrated in cerebral cortex-initiated without external stimuli-Can become reflexive-Muscle memory - developed when unconscious brain reproduce voluntary movements.

Rythmic movement-Walking/running-Combination of reflex/voluntary-Cerebral cortex initiates/terminates! Central pattern generators in-between— Animal paralyzed by spinal injury cannot initiate walk but if put on a treadmill CPGs will produce movement :)

! Maintnance of posture include all of the above mentioned movements

CNS integrates movementSpinal cord - integrates spinal reflexes and has CPGs - info from proprioreceptiosBrainstem/cerebellum - Central postural reflexes + hand/eye movement - info from proproiR(signals from vestibular apparatus co directly to cerebellum)Cerebral cortex/basal ggl - Voluntary movement

A pitcher decides ot throw a ballAP in interneurons of corticospinal tractMotor cortex -> spinal cord onto somatic MNContralaterall crossing in medullary pyramid (in pyramidal tract)->lateral corticospinal tract

Neurons from basal ganglia - extrapyramidal tractnoncrossing fibers - anterior corticospinal tract

ParkinssonProves basal ganglia has o role in body coordinationDisrupt in release of dopamine

Tetanus COntracted muscle paralysis by clostridium tetani.

Lecture CNS

-stimulus on free nerve endings -> graded potentials

Gray matter in CNS-cortex-nuclei-centers

White matter-tracts-columns - several tracts-Pathways - ascending and descending

PNS gray matter - gangliaPNS white matter - nerves

Divergence-broad distribution of specific input. pre and post

Convergence-several neurons synapse on same postsynaptic neuronsummation-> response

Serial processing neuron -> next neuronOne part of CNS to other

Parallell processingDivergence first then several neuronal pools process same information->many responses at the same time

Reverbeation1x neural pool/intermediate poolsends a positive feedback to keep chain of neurons active..Will continue into stimuli breaks/fatigue

Presynaptic inhibition3x target cellsOne has a inhibitory interneuron that synapses (hyper polarizing) -> no response in A->Response in B and C

Somatosensory pathway-Relayed ot brain/spinalcord via ascending pathways

Specific:1 typ of receptor1type of stimulusSpecific cortex areasNonspecificMore than one sensory unitTo brainstem, reticular formation, thalamus

FLowReceptor->1st order N(dorsal root ganglion)->2nd order N(spinal cord/brainstem)->3rd N(thalamus)->Somatosensory cortex(312)

Somatic part of sensory system transmit sensory information from skin, muscles, joints to CNS-all levels of spinal cord-reticullar formation, brainstem, midbrain-cerebellum,thalamus, somatosensory cortex

Receptors from dorsal rootPacinian corpuscle - vibration, pressure muchanoreceptorMuscle spindle, golgi tendon organEncapsulated endings! Free nerve endings form lateral division

Primary somatosensory cortex 312 postcentral gyrus parietal lobe+ sensory assosciation area

-ascending pathway in spinal cord - dorsal column (gracilis and cuneus)

Column in spinal cord - white matter (dorsal, ventral, lateral)Horn - gray matter (posterior, lateral, anterior)

Descenting tracts(motor)

Primary moter cortex, precentral gyrus € premotorcortex 6-> skeletal m. movement

Motor neurons in ventral horn of spinal cord

Direct pyramidal tract (corticospinal)-initiation on motor/premotor cortex-upper motor neuron motor cortex -> brainstem motor cortex -> spinal cord-lower motor neuron - alpha motor neuronsvoluntary movement and tone -only 3% Betz cells-80% cross at medullary pyramid -> lateral corticospinal tract-20% do not cross (eventually in spinal cord) -> anterior corticospinal tract. to postural muscles—most axons synapse with contralateral interneurons in spinal cord but some make monosynaptic connections to A/G motor neuronsBabinski respone -damage to corticospinal tract. Fanning of toes planter reflexCorticospinal - to muscles innervated by spinal motor neurons

Corticobulbar - motoroutput to muscles of face, tongue, throat

Indirect extrapyramidal tract-motor cortex-projections via brainstem nuclei-Neurons from basal ganglia - extrapyramidal tract-unconscious movemet - posture, balance-muccle toneRubrospinal tract - red nucleus. Flexors excitements, inhibit extensorzVestibulospinal tract - uncrossed bilateral - inc m. tone by gamma loop activation. no free fall while standing-Tectospinal tract - crossed-Terminates in spinal cord via interneurons which contact alpha and gamma motor neurons-Fibers which influence axial m. are crossed-Fibers for the limbs - mostly uncrossed->Permits independent control of the limbs and axial muscles.Manipulation can proceed while posture is maintained

Bell magendive lawAnterior/ventral spinal nerve roots = motorPosterior/dorsal nerve roots = sensory

The anterior spinal nerve roots contain only motor fibres and posterior roots only sensory fibres.

Stycknine poisoning - blocks inhibitory signals by competing with the inhibitory neurotransmitter glycine in spinal cord -> excitatory stateEasily activated muscles -> Muscle spasm. Death. In rat poising

glycine - inhibitory in spinal cordglutamate - excitatory

myotome same as dermatome but for motor output(muscle groups)

spinal schock - areflexiaearly - no stretch receptor, no sphincter tone, no sympathetic activity on smooth mlweeks - upper motor neuron signs develop, gradual reflex dec, some sphincter and ere tile, no voluntary control

Lessons from practice tests

Renshaw cells are inhibitory interneurons found in the gray matter of the spinal cord, and are associated in two ways with an alpha motor neuron.They receive an excitatory collateral from the alpha neuron's axon as they emerge from the motor root, and are thus "kept informed" of how vigorously that neuron is firing.They send an inhibitory axon to synapse with the cell body of the initial alpha neuron and/or an alpha motor neuron of the same motor pool.In this way, Renshaw cell inhibition represents a negative feedback mechanism. A Renshaw cell may be supplied by more than one alpha motor neuron collateral and it may synapse on multiple motor neurons.

-Renshaw cells act to inhibit sudden movements. Inhibit-inhibition af antagonistic muscle. -recurrent inhibition-control degree of efferent signal sent to the muscle -Descending cortical pathways modulate renshaw cells

Type 1a muscle fibers - in muscle spindle sensory. respond to change in length and velocitytype Ib in golgi tendontype II - fire when muscle is static

ATP is directly involved in relaxation of skeletal muscleActivation of renshaw cells -> increased permeability to Cl- ions and decreased AP in alpha motor neurons

The CSF has a lower glucose level than plasma

Alpha 2 motor neurons has low recruitment threshold - alpha 1 has high. Remember size principle - small motor unit and low threshold activated first.

Final motor pathway = alpha motor neuron and ad the end of that pathway we have: neuromuscular junction

Fast depolarization caused by voltage gates K+ channels ?

In monosynaptic spinal reflexestheir afferents and efferents are contained within same spinal nerve

the most used muscle fiber type in body areslow muscle fibers

flexion reflex involvesmore motor neurons than stretch reflex

activation of gamma motor neuronsstiumulates activation of alpha motor neurons

Inhibitorstetrodoxin(irriversible) - blocks Na+ channels - no APLidocaine(reversible) - blecks Na+ channels - no AP

Bartrachotoxin - opens Na+ channels irreversibly - blue froggy

Ach esterase breaks down acetylcholine to acetyl + cholineAch-esterase inhibitors ->spasm and hyperactivity of parasympathetic divisionIrreversible: flourophosphate, disopropylReversible neostygmine, phosphostygmine

Botulin - prevents release(exocytosis) of AchCurare - blocks the binding of Ach->no depolarizationStrychnine - inhibits glycine ”inhibits inhibition” -> excitation > uncontrolled convolusions and respiratory arrest. On frog on LABAtropne - blocks muscarinic receptors, inhibit parasympathetic neurons Ouabain - Na+/K+ ATPase inhibitor

! metroprolol - is B1 specific

neuron resting membrane potential = -70mVMuschle fiber resting membrane potential = -90mV

-Depolarization is not contraction!-ATP needed both for contraction and relaxation-Duration of AP in skeletal m. much shorter then duration of contraction - why summation is possible

https://www.dropbox.com/sh/7wd22woosu6ald2/AADtMrSAoLPmCyzXrAWhPy0Ya/physiology/Physio/PHYSIOTESTS/Physio/Tests%EF%80%A2Exams%205/PAT1/PAT1_-_summation.docx?dl=0

receptors sense a response via graded potentials

Somatotropic organization in ventral horn:

proximal muscles toward centerextensor most anteriorly

small MU - low threshold - activated firstslow MU fiber lower threshold

muscle tone cannot be voluntarily controlled

rubrospinal tract innervate flexor muscle - intact in decorticate but not decerebrate postion?

upper motor neuron damage - spastic, hyperreflexlower motor neuron - flaccid, no reflexes

Activation of renshaw cells-increased permeability of alphamMN to cl- ions

FALSElatency time of autonomic reflexes is the time needed for electromechanical coupling of ganglion cells

Skeletal m. has nicitinic cholinergic receptorsatropine block muscarinic

During normal movementred muscles fibers are recruited before white muscle fibers

In smooth m. increased levels of cAMP favors muscle relaxation

Labs

Human monosynaptic reflexes-Patellar-Achilles-Biceps and tricepsHuman polysynaptic-Flexion reflex-Abdominal reflex-Planter reflex(Babinski sign)

Propranolol test - proving parasympathetic influence on HRBeta blocker non selective