Axon, refractoriness

The excitable membrane of nerve axons, like the membrane of cardiac muscle (see Chapter 14) and neuronal cell bodies (see Chapter 21), maintains a resting transmembrane potential of -90 to -60 mV. During excitation, the sodium channels open, and a fast inward sodium current quickly depolarizes the membrane toward the sodium equilibrium potential (+40 mV). As a result of this depolarization process, the sodium channels close (inactivate) and potassium channels open. The outward flow of potassium repolarizes the membrane toward the potassium equilibrium potential (about -95 mV) repolarization returns the sodium channels to the rested state with a characteristic recovery time that determines the refractory period. The transmembrane ionic gradients are maintained by the sodium pump. These ionic fluxes are similar to, but simpler than, those in heart muscle, and local anesthetics have similar effects in both tissues. 

Neural transmission is also subjected to refractory periods in which further excitation of the postsynaptic neuron is not possible. In addition, varying types of nerve fibers (e.g., myelinated or demyelinated) exhibit differences in how the action potential moved down the axon, or in the speed of transmission of the action potential. 

Demyelination and axonal transection cause disruption in the transmission of nerve impulses, which leads to neurologic symptoms reflecting the area of the brain or spinal cord that is affected. De-myelinated nerve fibers have prolonged refractory periods that impair conduction of electrical impulse volleys. Maximal electrical impulse frequency may be reduced substantially before impulse conduction is interrupted entirely. A single plaque may extend across several nerve pathways, producing symptoms involving several nervous system functions. Smaller plaques may cause isolated disturbances however, typically several plaques develop at the same time, causing multiple but unrelated problems such as disturbed vision and decreased sensation. 

Because of the absolute refractory period of the voltagegated Na channels and the brief hyperpolarization resulting from efflux, the action potential Is propagated in one direction only, toward the axon terminus. 

After an impulse has passed, the region behind it in the axon is unable to transmit another impulse during a refractory period of several milliseconds. 

Properties of local anesthetics include all of the follovsdng EXCEPT (A) Blockade of voltage-dependent sodium channels Preferential binding to resting channels Slowing of axonal impulse conduction An increase in membrane refractory period Effects on vascular tone The pKg of lidocaine is 7.9. In infected tissue at pH 6.9, the fraction in the ionized form will be (A) 1%... 

Immediately after an impulse has been propagated, the axon is absolutely refractory, or completely inexcitable, and no stimulus, no matter how strong or long, can excite it. Shortly thereafter, the axon becomes relatively refractory it responds with a propagated impulse only to stimulation that is greater than the normal threshold. The length of the refractory period is affected by the frequency of stimulation and by many drugs (Fig. 16.5). 

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