1625915643-5d53d156c9525bd62bd0d3434ecdc231 (Netters - Essential Physiology (на английском)), страница 9

When a stimulus produces depolarizationthat reaches this threshold, voltage-gated Na+ channels open,and the inward flux of Na+ now exceeds the ability of K+leakage to maintain a steady state. The further depolarizationof the membrane opens more voltage-gated Na+ channels, andthis positive feedback continues until all voltage-gated Na+channels are open, producing the rapid, all-or-none depolar-ization characteristic of an action potential. These “fast channels” are rapidly inactivated as well.Along with these changes in Na+ conductance, there is adelayed, slower, and smaller increase in conductance of K+during the action potential (see Fig.

3.3). This is caused byopening of voltage-gated K+ channels, and along with the fallin Na+ conductance, is responsible for the repolarization ofthe membrane. These K+ channels remain open until themembrane finally returns to the equilibrium potential and aretherefore responsible for the hyperpolarization or “undershoot” phase of the action potential, during which the membrane is at a more negative potential than the resting potential.This “undershoot” contributes to the relative refractoriness ofthe membrane to generation of another action potential,because a greater stimulus will be required to displace thishyperpolarized membrane potential to the threshold potential.

A second factor contributing to refractoriness, earlier inthe relative refractory period, is that some Na+ channels stillremain inactivated.Extracellular Ca2+ concentration affects threshold potential byaltering the sensitivity of voltage-gated Na+ channels. At highCa2+ concentrations, greater membrane depolarization isrequired to activate the channels, and thus the excitability ofcells is reduced at high Ca2+ concentrations.An action potential is initiated in a cell when the membrane potential is sufficiently depolarized to reach thethreshold potential. When this occurs, opening of specificvoltage-gated channels results in increased conductance of oneor more ions, resulting in a rapid depolarization of the cell.

Inmany excitable cells, the upstroke of the action potential is aresult of opening of voltage-gated Na+ channels. When the cellreaches threshold potential, a sufficient number of activationgates of the Na+ channels are opened to allow Na+ flux throughthe membrane, which causes the upstroke of the action potential. Shortly thereafter, inactivation gates close the channels,terminating the upstroke. These inactivation gates remain openuntil the cell returns to the resting membrane potential.

Influxof K+ is responsible for repolarization of the membrane.ACTION POTENTIAL CONDUCTIONIn excitable cells, an action potential is rapidly propagated overthe cell membrane. In a neuron, when threshold potential isreached, an action potential is generated at the axon hillock,spreads to the axon, and is conducted to the axon terminal(Fig. 3.4) (conduction between cells is discussed later).

Asdepolarization occurs at a point on the membrane, Na+ flowsthrough the membrane from the extracellular fluid. Loss ofpositive charge at the point of depolarization causes local currents, in which positive charges flow from adjacent regionsalong the membrane to the area of depolarization (Fig. 3.5A).Local current results in depolarization of the adjacent regions;Nerve and Muscle PhysiologyARP20RRPAction potentialMembrane potential (mV)0Na conductanceK conductance70msec00.51.0MembraneExtracellularfluidNaⴙNaKClAxoplasmKⴙCl40StimuluscurrentNaⴙNaⴙKClKⴙCl20At firing level, Naⴙ conductance isgreatly increased, giving rise tostrong inward Naⴙ currentNaNaⴙKClKⴙCl75Naⴙ conductance returns to normal;Kⴙ conductance increases, causinghyperpolarizationStimulus currentproduces depolarization20Stim.NaⴙNaⴙClⴚClⴚClⴚKⴙKⴙKⴙNaⴙ75Equivalent circuit diagramsFigure 3.3 Action Potential The action potential in most excitable cells is initiated when a localpotential on a cell reaches a threshold at which voltage-gated Na+ channels open, greatly increasing Na+conductance.

Changes in Na+ and K+ conductance during the action potential are illustrated, along with theequivalent circuit diagrams.2930The Nervous System and MuscleDendritesDendritic spines(gemmules)Rough endoplasmicreticulum (Nissl substance)RibosomesMitochondrionNucleusAxonNucleolusAxon hillockInitial segment of axonNeurotubulesGolgi apparatusLysosomeCell body (soma)Axosomatic synapseGlial (astrocyte) processAxodendritic synapseFigure 3.4 Neurons Neurons consist of the soma (cell body), multiple dendrites, and an axon.

Neuronsreceive signals from other neurons at synapses, resulting in changes in local membrane potential. When themembrane potential is sufficiently depolarized, an action potential is initiated at the axon hillock and ispropagated down the length of the axon to synapses with other neurons or muscle cells.when threshold is reached, the action potential is propagated.An important characteristic of action potential propagation isthat it occurs away from the point of initiation; it cannot travelback toward its origin.

As the action potential is conducted,the area of the membrane directly behind the action potentialis still in the absolute refractory state due to Na+ channel inactivation, preventing retrograde conduction.potential to change to 63% of its final value when a current isapplied is τ (t = Rm ¥ Cm). It is a measure of how slowly orquickly the membrane depolarizes or repolarizes, and is therefore inversely related to action potential conduction velocity.Because τ is inversely related to conduction velocity, lowmembrane resistance and low membrane capacitance favorfaster conduction.An essential property of neurons is the ability to rapidly propagate an action potential, analogous to an electrical cable.Conduction velocity is a function of:The space constant (λ, also known as the length constant) isthe distance along the membrane over which a potential changewill fall to 63% of its value, and therefore describes how far adepolarizing current will spread.

With greater λ, depolarizingcurrents will spread further, resulting in greater conductionvelocity. λ is proportional to the ratio of Rm to Ri:■■■Internal resistance (Ri), the impedance to current flowwithin the cytoplasm (for example, resistance within theaxon).Membrane resistance (Rm), the impedance to currentflow through the membrane.Capacitance (Cm), the ability of the membrane to storecharge.The relationships between these variables result in the cableproperties of cells: the space constant (λ) and the time constant (τ), which are useful in describing conduction of electrical activity in an axon.

The time it takes for membraneλ = (Rm Ri )The importance of internal resistance (Ri) in actionpotential conduction velocity can be inferred from theanatomy of axons of large invertebrates. The giant axon of thesquid has a diameter of 500 μm; with this increased diameter,λ is high because Ri is low, resulting in the rapid conductionnecessary in a large animal.Nerve and Muscle PhysiologyA. Unmyelinated fibersⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴚⴙⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴙⴚⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙⴚⴙAxolemmaB. Myelinated fibersⴙⴚⴚⴙⴙⴚAxoplasmImpulseⴚⴙⴚⴙⴚⴙNode of RanvierMyelin sheathC.

Classification of nerve fibers by size and conduction velocity120Myelinated fibersEfferent110100Alpha motor neurons to extrafusal striated(somatic) muscle fibers (motor endplates)Afferent908070Conductionvelocity60(m/sec)504030Gamma motor neuronsto intrafusal fibers of spindlesin striated muscleAutonomicpreganglionic(group B) fibersGroup II (A fibers) from secondary endings ofmuscle spindles: proprioception; from specializedreceptors in skin and deep tissues: touch, pressureAutonomicpostganglionic(group C)fibersGroup III (A fibers) from free and from some specialized endingsin muscle and joints: pain; from skin: sharp pain, heat, cold, andsome touch and pressure; also many visceral afferents2010Group I (A fibers) Ia from primary musclespindle endings: proprioception; lb fromGolgi tendon organs: proprioceptionUnmyelinated fibersGroup IV (C fibers) from skin and muscle: slow burning pain; also visceral pain510Fiber diameter (microns)1520Figure 3.5 Axonal Conduction A, An action potential is propagated and conducted along an axonas adjacent portions of the membrane are depolarized by local currents.

B, In myelinated axons, the actionpotential “jumps” between nodes of Ranvier. This process, called saltatory conduction, greatly increasesconduction velocity. C, Myelination and axonal diameter are associated with higher conduction velocity.3132The Nervous System and MuscleThe nervous system of vertebrates is much more complex andcomposed of a much larger number of neurons than that ofinvertebrates. Many nerve cells in the vertebrate nervoussystem are myelinated (Fig.

3.5B). They are covered by multiple layers of an insulating sheath of phospholipid membrane, formed by Schwann cells in the peripheral nervoussystem and oligodendrocytes in the central nervous system.This insulation greatly decreases capacitance and also increasesmembrane resistance, such that current travels through theinterior of the axon, but not across the membrane. To allowpropagation of the action potential, there are breaks in themyelin sheath called nodes of Ranvier. They are present at1 to 2 mm intervals along the axon, and the actionpotential thus “jumps” rapidly from node to node, bypassingCLINICAL CORRELATEMultiple SclerosisMultiple sclerosis (MS) is an inflammatory neurodegenerativedisease, believed to be of autoimmune etiology.

It is more commonin women than men, and the usual age of onset is between 20 and40 years of age. The inflammatory process of MS results in thegradual destruction of myelin sheaths around myelinated axonsof the brain and spinal cord. A wide variety of symptoms mayoccur, including muscle weakness and paralysis; impaired coordi-the myelinated areas. Essentially, the nodes of Ranvier represent multiple capacitors in series.

This process of conductionwhereby the action potential “jumps” between nodes is knownas saltatory conduction and allows very rapid propagation ofthe action potential, despite small axon diameter. Local currents generated at one node during depolarization result indepolarization at the next node, and the action potential skipsalong the axon, bypassing the highly insulated segments.Fibers throughout the nervous system vary in terms of diameter and conduction velocity and may be classified into varioustypes on this basis (Fig.