Nervous Physiology and Neurotransmitters

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    Chapter 12: Nerve Physiology and Neurotransmitters

    1. What are the processes that contribute the resting membrane potential (RMP) in nervesand what precisely is the value of RMP in mV?

    The resting membrane potential exists because electrolytes are unequally distributed

    between the ECF and the ICF1. Three factors collectively determine the RMP:

    a. Diffusion of ions down their concentration gradients through the

    membrane.b. Selective permeability of the membrane, allowing some ions to pass

    more easily than others.

    c. Electrical attraction of cations and anions to each other.

    The resting membrane potential is -70 mV.

    2. What is the concentration of sodium and potassium ions inside and outside the neuron at

    RMP?

    a. Potassium ions (K+

    ) have the greatest influence on RMP because the plasma ismore permeable to K+ than to any other ion.

    i. Many cytoplasmic anions cannot escape from the cell because of their sizeor charge, so that diffusion of K+ out of the cell down its concentration

    gradient leaves the ICF with a net negative charge.

    ii. The negative ICF attracts K+ back into the cell, so that eventuallyequilibrium is reached between concentration-driven diffusion and

    electrical attraction; at this point, the net diffusion of K+ stops.

    iii. At equilibrium K+ is 40 times as concentrated in the ICF as in the ECF.

    iv. If K+ were the only ion involved, the RMP would be about 90 mV.b. Sodium ions (Na+) also influence the RMP.

    i. Na+

    is 12 times more concentrated in the ECF than in the ICF.ii. Although the resting membrane is less permeable to Na+, it does diffuse

    down the concentration gradient into the cell and is attracted by the anions

    of the ICF.

    3. How much does the sodium potassium pump contribute to the RMP?

    a. The Na+K+ pump continually compensates for the leakage of Na+ and K+ into and

    out of the cell.b. For every 1 ATP consumed by the Na+K+ pump, 3 Na+ are pumped out of the

    cell and 2 K+ are brought in.

    c. The Na+K+ pump accounts for about 70% of the ATP requirement of the nervous

    system and it works continually, which is why the nervous system consumes somuch glucose and oxygen.

    d. The net effect of K diffusion outward, Na diffusion inward, and the action of the

    NaK pump is the RMP of 70 mV.

    4. What is an action potential? Discuss the process in detail covering the events in order of

    occurrence and the direction of ion flow.

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    7. What is meant by the threshold for an action potential?

    For anything to happen, local potential must rise to a critical voltage called thethreshold (typically about -55 mV) and is the minimum needed to open voltage-regulated

    gates.

    8. Describe how the concentration of voltage gated channels varies along the length of a

    myelinated axon.

    In myelinated fibers, voltage-regulated ion gates are scarce in the myelin-

    covered internodes (fewer than 25/m2 compared with 2,000 to 12,000/m2 in

    nodes of Ranvier).a. A nerve signal travels through an internode as Na+ diffuses down the

    fiber under the axolemma; this flow is very fast but is decremental.

    b. A node of Ranvier occurs every millimeter or less along the axon,however, with an abundance of voltage-regulated gates.

    c. When the diffusing ions reach a node, these gates are opened and a new

    action potential is generated; this process of jumping from node to node is

    called saltatory conduction.

    9. What is depolarization?

    It refers to any situation in which the membrane voltage shifts to a less negative value.

    10. What is the refractory period, both absolute and relative?

    The period of resistance to re-stimulation is called the refractory period

    Absolute refractory period: no stimulus of any strength will trigger a new

    action potential

    Relative refractory period: possible to trigger a new action potential, butonly with an unusually strong stimulus.

    11. What is salutatory conduction and how does it affect the conduction velocity of an axon?

    Process of jumping from node to node is called saltatory conduction.

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    Voltage-regulated ion gates are scarce in myelin-covered internodes than at nodes of

    Ranvier.

    The only way a nerve signal can travel along an internode is for Na that enters at the

    previous node to diffuse down the fiber under the axolemmaa very fast processnerve

    fiber resist processconduction is decremental

    Fortunately there is node of Ranvier every millimeter, where it is exposed to ECF andthere is abundance of voltage-regulated gates.

    Internodes, saltatory conduction based on process that is very fast but decremental

    Nodes, conduction is slower but non-decremental.

    Since most of the axon is covered with myelin, conduction occurs mainly by fast

    diffusion.

    12. What are the different classes of neurotransmitters? What are the representative

    neurotransmitters of each class?

    13. How does GABA perform its inhibitory function?

    a. GABA-ergic synapse employs -aminobutyric acid as its neurotransmitter; in aninhibitory synapse:

    i. The release of GABA by the presynaptic neuron and its binding to ion

    gates is a similar mechanism as for cholinergic synapses.ii. The GABA receptor, however, is a chloride channel, and when it opens,

    Cl enters the cell, increasing the negative membrane potential and

    inhibiting firing.

    14. Understand the basics of excitatory adrenergic synapse.

    a. An adrenergic synapse employs norepinephrine (NE) as a neurotransmitter; itsreceptor is not an ion gate but a transmembrane protein associated with a Gprotein in a second-messenger system. (Fig. 12.23)

    b. Binding of NE to the recetpro causes the G protein to dissociate from it.

    c. The G protein binds to adenlyate cyclase, inducing it to convert ATP to cyclicAMP (cAMP).

    d. Cyclic AMP can induce several alternative effects inside the cell.

    e. One effect is to produce an internal chemical that binds to a ligand-regulated iongate from inside the membrane, opening the gate.

    f. Another is to activate preexisting cytoplasmic enzymes that affect metabolism.

    g. Yet another is to induce genetic transcription, so that new enzymes are produced.

    15. What are the methods by which signals are turned off that where stimulated by

    neurotransmitters?

    a. The cessation of action potentials in the presynaptic nerve fiber stop the release ofneurotransmitter.

    b. The removal of neurotransmitter from the synaptic cleft is accomplished in three

    ways.

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    i. Diffusion. Neurotransmitter leaves the synapse and enters the ECF. In the

    CNS, astrocytes absorb it and return it to neurons.

    ii. Reuptake. The synaptic knob reabsorbs amino acids and monoamines byendocytosis and breaks them down with monoamine oxidase (MAO).

    iii. Degradation. The enzyme acetylcholinesterase (AChE) breaks down ACh

    into acetate and choline, the latter of which is reabsorbed by the synapticknob.

    16. What is the advantage for a neuron having a greater number of synapses?

    It affords greater information-processing capabilities.

    17. What is an EPSP? Which ions are involved?

    Any voltage change in the direction that makes a neuron more likely to fire

    Usually result from Na flowing into the cell and canceling some of the negative charge

    on the inside of the membrane.

    18. What is an IPSP? Which ions are involved?Neurotransmitter hyperpolarizes the postsynaptic cell and makes it more negative than

    the RMP, making the postsynaptic cell less likely to fire.

    Produced by neurotransmitter opening ligand-regulated chloride gates, making the

    cytosol more negative.

    Less common way is to open selective K gates, increasing K diffusion out of the cell.

    19. Understand temporal summation as compared to spatial summation in triggering

    postsynaptic potentials?

    Temporal Summation Spatial Summation

    A single presynaptic neuron stimulates the

    postsynaptic neuron so intensely that itsEPSPs add up to threshold and make it fire

    Multiple inputs to the postsynaptic cell

    each produce a moderate amount ofstimulation, but collectively produce

    enough EPSPs to add up to threshold at thetrigger zone and make the cell fire.

    20. What is presynaptic inhibition?

    Is the opposite of facilitation, a mechanism in which one presynaptic neuron

    suppresses another oneused to halt unwanted synaptic transmission.

    21. Understand the conditions of Alzheimers disease and Parkinsons disease to the detail

    covered in lecture and in your textbook

    Alzheimers Disease:a. One of first symptoms is memory loss, especially for recent events

    i. Ask the same question repeatedly

    ii. Reduced attention spaniii. Become disoriented and lost in previously familiar places

    iv. Become moody, confused, paranoid, and combative

    b. Loss ability to read, write, talk, walk and eat

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    c. Death ensues from pneumonia or other complications of confinement and

    immobility.

    d. Diagnosis can be confirmed by autopsyi. Atrophy of some of the gyri (folds) of the cerebral cortex and

    hippocampus, an important center of memory.

    ii. Nerve cells exhibit neurofibrillary tanglesiii. Intercellular spaces, there are senile plaques consisting of aggregations of

    cells, altered nerve fibers and a core of beta amyloid proteinthe

    breakdown product of a glycoprotein of plasma membranes.e. Three genes on chromosomes 1, 14 and 21 have been implicated in various forms

    of early and late onset AD.

    f. Treatment focuses on trying to halt beta amyloid formation or stimulate immune

    system to clear beta amyloid from brain tissue.i. AD patients show deficiency of acetylcholine and nerve growth factors.

    Parkinsons Disease

    Also called paralysis agitansA progressive loss of motor function beginning in the 50s and 60s.

    c. c. Due to degeneration of dopamine-releasing neurons in portion of brain called thesubstantia nigra.

    d. d. Dopamine is an inhibitory neurotransmitter that normally prevents excessive

    activity in motor center of brain called basal nuclei

    1. Degeneration of dopamine-releasingneurons leads to an excessive ratio of ACh to DA, causing

    hyperactivity of the basal nuclei.

    2. Suffer involuntary muscle contraction3. Facial muscles become rigid

    4. Speech slurred

    5. Walks slowly with shuffling gaitg. Treatment with dopamine is ineffective because it cannot cross the blood brain

    barrier

    i. Precursor L-dopa does cross the barrier and used to treat PD1. Relieves the symptoms but does not slow progression of disease.

    ii. Newer Drug deprenyl, a MAO inhibitor that retards neural degeneration

    and development of symptoms

    iii. Surgical technique called pallidotomy used to quell severe

    tremorsdestruction of small portion of cerebral tissue in area called

    globus pallidus.

    iv. Subthalamic nucleus and ventral intermediate nucleus are brain areas thatare targeted and involve either the destruction of tiny areas of tissue or the

    implantation of stimulating electrodes.

    a.