Unit VELECTROPHYSIOLOGY

Chapter 11 pp. 396-424

E. Gorski/ E. Lathrop-Davis/ S. Kabrhel

Biology 220Anatomy & Physiology I

Plasma MembraneMembrane potential = electrical voltage difference

across plasma membrane of cell• caused by differences in ion concentrations

maintained by plasma membrane proteinsMembrane structure• phospholipids• integral proteins - form channels

Fig. 11.6, p. 397

Review chapter 3 (pp. 68-80): membrane structure, transport

Membrane ChannelsTwo major classes of channels:1. Leakage channels (non-gated or passive channels)

° always open° more K+ than Na+ channels

- allow influx of Na+, efflux of K+

° found in cell body and dendrites2. Gated channels

° open/close based on environment° found in cell body, dendrites, axon hillock,

unmyelinated axons and myelinated axons (nodes of Ranvier)

Fig. 11.6, p. 397

Types of Gated Channels• chemically gated* -- respond to neurotransmitters, hormones, ions (e.g,. H+, Ca2+)° found in cell bodies and dendrites

• voltage gated* -- respond to change in membrane potential° found in axon hillock, axon

• mechanically gated -- respond to mechanical change (vibration, pressure, stretch; e.g., stretch or touch receptors)

Resting Membrane Potential (RMP)Intracellular environment different from extracellular environment in ionic composition

Inside:more K+, protein (anion)

Outside:more Na+, Cl-

Fig. 11.8, p. 398

Negative inside compared to outside; RMP = -70 mV

Resting Membrane Potential (RMP) • cell membrane with a potential (difference in voltage

across membrane) is polarized• in neuron, at rest:

° inside: more K+, protein (anion)- K+ diffuses out of cell through open K+/ Na+

channels ° outside: more Na+, Cl-

- Na+ diffuses into cell through open K+/ Na+

channels° ion gradients (necessary for passive moment of

ions) maintained by Na+/K+ pump (active transport system)

See also Chapter 3, pp. 81-83

Sodium-Potassium (Na+/K+) Pump

Fig. 3.9, p.76Active transport (requires ATP)

• uses transport protein in membrane (Na+/K+ Pump)

• moves 3 Na+ out of cell; 2 K+ into cell

Diffusion

Diffusion

• sets up and maintains ion gradients necessary for diffusion

Types of PotentialsGraded Potential• magnitude varies with stimulus

° more depolarization with stronger stimulus° decays away from point of stimulus

Action Potential• magnitude stays the same• once started, passes along axon as nerve impulse

Graded Potential• magnitude varies with stimulus --> allows graded

responses• localized• short-lived• membrane may be:

° hyperpolarized (more negative than resting potential; caused by influx of Cl- efflux of K+), or

° depolarized (less negative than resting; caused by influx of Na+)

• at receptor = receptor potential• at synapse = synaptic potential

Depolarization and Hyperpolarization

Fig. 11.9, p. 399

Graded Potential• depolarization starts at area

of stimulus• spreads by ions moving on

either side of membrane (not from outside to inside)

• larger stimulus opens more channels

• if membrane reaches threshold (~ -50 to -55 mV), action potential (AP) will be initiated

Fig. 11.10, p. 400

Action Potential• membrane potential goes from -70 mV to +30 mV

then back to -70 mV (after hyperpolarization)• all-or-none principle:

° either start and pass AP, or don’t° continues once started

• passed through membrane of excitable cells (neurons and muscles)° called nerve impulse when passed through axon

Action Potential (con’t)• long-distance communication• propagation is unidirectional (one direction away

from point of stimulation)• includes depolarization, repolarization and

undershoot (hyperpolarization)° depolarization: -70 mV to +30 mV

- based on influx of Na+

° repolarization: +30 mV to -70 mV- based on efflux of K+

° undershoot (hyperpolarization): -70 mV to -90mV - potassium permeability continues

Events of an Action Potential

Fig. 11.12, p. 402

AP: Depolarizationstimulus

chemically-gated Na+ channels open

Na+ influx

graded depolarization of dendrite or cell body

spreads to axon hillock, if threshold reached voltage-gated Na+ channels open (#2 in figure)

Na+ influx (positive feedback)

timed gates on Na+ channels close, K+ channels open for repolarization

See Fig. 11.12, p. 402

AP: RepolarizationNa+ channels closed, gated K+ channels open

K+ leaves cell taking + charge with it repolarization (#3)

goes past normal resting potential (hyperpolarization) (#4)

gated K+ channels close

Na+/K+ pump returns Na+/K+ levels to resting

See Fig. 11.12, p. 402

AP: Refractory PeriodTime during which

neuron membrane does not respond normally to additional stimuli

• Absolute refractory period: time in which a new AP cannot be started

• Relative refractory period: time in which new AP can only be started by stronger stimulus

Fig. 11.15, p. 405

Comparison of Graded andAction Potentials

Graded Potential Action PotentialCharacteristic

Variable Always the same (all-or-none)Amplitude

Variable (depends on stimulus)

Rapid membrane changeDuration

Chemically- or mechanically-gated

Voltage-gatedChannels

Localized (short-distance) Transmitted along axon as impulse

Propagation

None (allows summation) Absolute (no new APs); Refractory (only with stronger stimulus)

Refractory period

Depolarization or hyperpolarization

Depolarization, followed by repolarization and hyperpolarization

Membrane voltage change

Dendrites, perikaryon Axon hillock, axonLocation

Impulse Conduction• action potential (AP) passed through the axon as

an impulse• “Rapid, transient, self-propagating reversal in

membrane potential” Raven & Wood, 1976

• two types of conduction:° continuous° saltatory

direction is one-way due to absolute refractory period shown in light blue

Continuous Impulse Conduction• involves passage of AP

along entire membrane• occurs in unmyelinated

axons and muscle fibers• depolarization/

repolarization occurs in step-wise manner as Na+ and K+ channels open and close in adjacent parts of membrane

Fig. 11.13, p. 404

Saltatory Conduction• AP passed from one node of Ranvier to the next• occurs in myelinated fibers• saves ATP (Na+/K+ pump only used at nodes)• faster

Fig. 11.16, p. 406

Fig. 11.14, p. 405

Stimulus Intensity• affects number of impulses sent per unit time• does not affect velocity of conduction• also affects number of neurons involved

Factors Influencing Impulse Conduction: Intrinsic Factors

1. Fiber diameter° larger (thicker) is faster (because of lower

resistance)2. Degree of myelination

° myelinated fibers are quicker because of saltatory conduction

° multiple sclerosis – degenerative autoimmune disease in which myelin sheaths of CNS are destroyed by person’s own antibodies

Factors Influencing Impulse Conduction: Intrinsic Factors

3. Three groups of fibers:° A° B° C

• Groups based on:° diameter° degree of myelination

Fiber Types - Group A

• Group A (fastest): ° largest diameter (thickest)° thick myelin sheath° conduction velocities of 15-150 m/s° include somatic motor and some somatic

sensory (from skin, skeletal muscles and joints - touch, pressure, hot/cold, stretch, tension)

Fiber Types - Group B & C• Group B (intermediate):

° intermediate diameter° thin myelin sheath° conduction velocities of 3-15 m/s

• Group C (slowest): ° small diameter° no myelin sheath (continuous conduction)° conduction velocities of 1 m/s, or less

• Group B & C include:° autonomic NS motor fibers to viscera° sensory fibers from viscera° small somatic fibers from skin (pain, some

pressure and light touch receptors)

Factors Influencing Speed of Conduction: Extrinsic Factors

Factors other than axon itself1. temperature – due to general influence of heat on

chemical reactions° warmer goes faster° colder goes slower

2. pH° decreased pH < 7.35 (increased H+)

decreased excitability (depression)° increased pH > 7.45 (decreased H+)

increased excitability

Extrinsic Factors (con’t)3. excessive or prolonged pressure (interrupts blood flow)4. inhibitory chemicals reduce membrane permeability to

Na+ (harder to depolarize) ° alcohol, sedatives, anesthetics

5. excitatory chemicals cause easier depolarization° caffeine, nicotine

6. Ca2+ levels° low Ca2+ - increases excitability° high Ca2+ -decreases excitability

Synapses• junctions between neurons at which information is

passed from one neuron (presynaptic neuron) to another (postsynaptic neuron)

• junction between neuron and effector (muscle or gland) usually called neuroeffector junction (NEJ)° neuromuscular junction (NMJ)

- neuron to muscle° neuroglandular junction (NGJ)

- neuron to gland

Structure of Distal End of Axon• telodendria – terminal branches of axon

° allow axon to contact more than one cell or one cell in several places

• axonal terminals = synaptic end bulbs° contain neurotransmitter (or gap junctions)

• synaptic cleft – space between presynaptic and postsynaptic membranes

See Figure 11.18, p. 409

See Fig. 11. 17, p. 408

Types of SynapsesDefined by:1. location: where signal comes from (e.g., axon) to

where it goes (e.g., dendrite, muscle)2. how signal is transferred

a. based on location:° neuron-neuron° neuron-muscle° neuron-gland

b. based on method of information transfer:° electrical synapses° chemical synapses

Synapse LocationsBased on locations, most common are:• axodentritic = axon (presynaptic) to dendrite

(postsynaptic)• axosomatic = axon (presynaptic) to cell body, or

soma (postsynaptic)• axoaxonic = axon (presynaptic) to axon or axon

hillock (less common than the other 2)Fig. 11.17, p. 408

Electrical Synapses• less common type of synapse• joined by gap junctions• cells said to be “electrically coupled”• very rapid transmission• excitatory only• allow bi-directional flow• importance:

° allow synchronization of neuronal firing (important to stereotypical behavior)

° important during development of nervous system (later, most replaced by chemical synapses)

• also present in visceral smooth muscle, cardiac muscle

• axonal terminal of presynaptic neuron releases neurotransmitter (NT) from synaptic vesicle into synaptic cleft

• postsynaptic membrane (of neuron or effector) contains receptors that recognize NT

• slower than electrical• unidirectional (one way)• inhibitory or excitatory• found at:

° most neuron-neuron synapses

° neuroeffector junctions

Chemical Synapses

Fig. 11.18, p. 409

Events at Chemical Synapse1. impulse within presynaptic neuron reaches axon

terminal, depolarizes membrane voltage-gated Na+ and Ca2+ channels open in presynaptic membrane --> Ca2+ enters cell

2. entrance of Ca2+ into cell signals synaptic vesicles to fuse with axonal plasma membrane for release of NT into synaptic cleft (exocytosis)

Fig. 11.18, p. 409

See A.D.A.M.Nervous System IICD

Events at Chemical Synapse (con’t)

3. NT diffuses across synaptic cleft4. NT binds to its specific receptor on postsynpatic

membrane5. ion channels open in postsynpatic membrane

allowing ion movement

Fig. 11.18, p. 409

See A.D.A.M.Nervous System IICD

Postsynaptic Potentials and Synaptic Integration

• transmission from presynaptic to postsynaptic neuron is excitatory or inhibitory depending on type of NT released° each presynaptic neuron releases either

excitatory NT or inhibitory NT• postsynpatic membranes normally dendrite or cell

body (soma or perikaryon)

Postsynaptic Potentials and Synaptic Integration

• reaction of receptors to NTs is graded, response depends on number of receptors involved (which depends on amount of NT released)° excitatory postsynaptic potentials (EPSPs)° inhibitory postsynaptic potentials (IPSPs)

Excitatory Synapses and EPSPs• binding of NT released by presynaptic membrane to receptor (on

postsynaptic membrane) causes opening of membrane channels that allow both Na+ and K+ to diffuse across postsynaptic membrane

• because more Na+ enters than K+ leaves --> net depolarization

• local graded excitatory postsynaptic potential (EPSP)

• if EPSP is sufficiently large, may spread to axon hillock leading to AP

Excitatory Synapses and EPSPs

Fig. 11.19, p. 410

Inhibitory Synapses and IPSPs

Fig. 11.19, p. 410

• binding of NT released by presynaptic membrane to receptor (on postsynaptic membrane) causes opening of membrane channels that allow K+ to diffuse out of post-synaptic cell, or Cl- to diffuse in, or both

• causes hyperpolarization

Modification of Synaptic EventsTemporal summation

• 1 or more presynaptic neurons fire before 1st EPSP fades

• if summed EPSP is large enough, then get AP

Fig. 11.20, p. 412

Modification of Synaptic EventsSpatial summation• large number of axonal terminals from different

neurons or the same neuron fire at the same time• if EPSP is large enough, then get AP

Fig. 11.20, p. 412

Spatial Summation EPSP and IPSP• IPSP and EPSP have opposite effects• if only IPSPs occur, postsynaptic membrane becomes

hyperpolarized° effects of IPSP may be temporally or spatially

summed• usually IPSPs prevent membrane from becoming as

depolarized as it would with only EPSPs

Fig. 11.20, p. 412

Synaptic Potentiation and Facilitation

• synaptic potentiation: presynaptic axonal terminal that has received repeated (in short period of time) or continuous stimulation contains more intracellular Ca2+ than normal triggers greater release of NT into synaptic cleft --> produces larger EPSP in postsynaptic cell(important in memory and learning processes)

• facilitation: postsynaptic neuron that has been partially depolarized is more likely to undergo AP,

Termination of NT Effects

1. removal from cleft by reuptake into astrocytes or presynaptic membrane (e.g., norepinephrine)

2. degradation of NT by enzymes present in postsynaptic membrane or synaptic cleft

• e.g., acetylcholine [ACh] degraded by the enzyme acetylcholinesterase - [AChE]

3. diffusion away from cleft

Functional Classification ofNeurotransmitters (NTs)

A. Based on effects° excitatory – cause depolarization (glutamate)° inhibitory – cause hyperpolarization (GABA)° effect of some depends on postsynaptic

membrane receptors- ACh and NE have different receptor types –

some that cause excitation and other types that causes inhibition

B. Based on mechanism of action° direct (channel-linked receptors)° indirect (G protein-linked receptors = second

messenger system)

Modes of Action: Direct Action

• open ion channels • immediate and localized

action• action depends on binding

of NT to receptors followed by channel activation, ion influx and membrane potential changes

• excitatory examples: aspartate, acetylcholine (ACh), glutamate, ATP*open Na+/K+, Ca2+

channels leading to depolarization

• inhibitory examples: gamma aminobutyric acid (GABA), glycine *open Cl- or K+ channels

leading to hyperpolarization

Fig. 11.22, p. 418

Modes of Action: Indirect Action• slower, longer-lasting effects• work through second messengers

° binding of NT with receptor activates G protein in membrane which works through cyclic AMP (cAMP = second messenger) to:- regulate ion channels (open or close)- activate kinase enzymes within cytoplasm

(activate proteins in cytoplasm)

Modes of Action: Indirect ActionExamples• Biogenic amines (dopamine, norepinephrine, epinephrine)• Peptides (endorphins, dynorphins, substance P)• ACh (at muscarinic receptors)

Fig. 11.22, p. 418

Structural Classes of Neurotransmitters

• Classified according to chemical structure:° Acetylcholine (ACh)° Biogenic Amines° Amino Acids° Peptides° Novel Messengers

Acetylcholine (ACh)

• first NT to be discovered• excitatory to skeletal muscles• excitatory/inhibitory to viscera• found in CNS and PNS (NMJ with skeletal muscle,

NEJ for parasympathetic nervous system)• formed from acetyl-CoA and choline• degraded by acetylcholinesterase (AChE)• Myasthenia gravis - autoimmune disorder of

skeletal muscle ACh receptors• Alzheimer’s disease - decreased ACh level in brain

that ultimately results in mental deterioration

Biogenic Amines• synthesized from amino acid tyrosine• found in CNS and PNS

° catecholamines - norepinephrine [NE], epinephrine, dopamine, - excitatory or inhibitory

° indolamines - seratonin and histamine- generally inhibitory

• play role in emotional behavior and help regulate biological clock; norepinephrine is main NT of sympathetic division of ANS

• schizophrenia - overproduction of dopamine• Parkinson’s disease - deficient dopamine in basal

ganglia

Amino Acids & Peptides

• Amino Acids° GABA = gamma amino butyric acid (principal

inhibitory NT in brain), ° glycine (generally inhibitory NT, in spinal cord),° glutamate (CNS, excitatory)

• Peptides (Neuropeptides)° strings of amino acids produced in CNS and PNS:

- endorphins and enkephalins (natural opiates)- substance P (mediator of pain signals)

° some also produced by nonneural tissues (e.g., cells of GI tract - somatostatin, cholecystokinin, vasoactive intestinal peptide [VIP])

Novel Messengers Neurotransmitters that don’t fit other categories• NO = nitric oxide

° involved in long-term synaptic potentiation (learning and memory)

° relaxation of intestinal smooth muscles ° responsible for brain damage in stroke patients

• ATP = adenosine triphosphate ° promotes synthesis and uptake of other NTs in CNS

and PNS• CO = carbon monoxide

° enhances neurotransmission in some circuits involved in logic

° regulator of cyclic GMP (second messenger)

Organization of Neurons:Types of Circuits

• Simple series circuit• Converging circuit• Diverging circuit• Reverberating (oscillatory) circuit• Parallel after-discharge circuit

Fig. 11.25, p. 421

Simple Series Circuit

• one presynaptic neuron goes to one postsynaptic neuron; e.g., simple reflex arc

presynaptic

postsynaptic

synapses

Converging Circuits

• several presynaptic axonal terminals go to single postsynaptic neuron (output)

• input from several pathways produces single result

• e.g., voluntary vs sub- conscious breathing; “happy baby”

Fig. 11.24, p. 420

Diverging Circuits • one presynaptic neuron --> several postsynaptic

neurons• e.g., single motor neuron from brain may go to

several motor neurons in spinal cord (thence to several muscle fibers)e.g., single sensory neuron to CNS may be part of reflex but also send info to brain

Fig. 11.24, p. 420

Reverberating (Oscillatory) Circuits • chain of neurons with synapses to neurons earlier

in circuit° sleep-wake cycle° breathing° possibly short-term memory° some motor activities (arm swinging)

Fig. 11.24, p. 420

Parallel After-Discharge Circuit • one presynaptic neuron fires to several

postsynaptic neurons arranged in parallel that eventually result in common output

• many different responses occur simultaneously° may be involved in problem solving

Fig. 11.24, p. 420