Sodium inactivation, nerve cells

Veratrum alkaloids cause repetitive discharges of nerve cells, apparently by delaying repolarization (possibly by action on lipid components and an ATPase in the cell membrane) (Levinson, 1976). Veratridine (94) binds to the sodium channel and keeps it permanently open and active (Greenhill and Grayshan, 1992). Protoveratrines A and B inhibit inactivation of Na channels. Cevadine (95) and protoveratrines A and B (85,86) depolarize membranes (Wink, 1993). 

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. 

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