The Role of Slow Potassium Current in Phenomena of Voltage-Dependent Action of 4-Aminopyridine in Amphibian Myelinated Nerve Fibres

摘要

The mechanism underlying the voltage-dependent action of 4-aminopyridine (4-AP) is investigatedin experiments on amphibian myelinated nerve fibres (Rana ridibunda Pallas) by way of extracellular recordingof electrical activity and using activators of potassium current (potassium-free solution and nitric oxide NO)and inhibitors of sodium current (tetrodotoxin). Measurement of action potential (AP) areas was used to eval-uate the extent of general membrane depolarization during the activity of nerve fibres. Tetrodotoxin-induceddecrease in general membrane depolarization (when the action potential amplitude was reduced by less than20%) leads to an increase in the duration of depolarizing after-potential (DAP). This supports the dependenceof time course of DAP in the presence of 4-AP on ratio of fast and slow potassium channels. In the absence of4-AP, potassium-free solution and NO increase the potassium current through fast potassium channels (decreas-ing AP duration, reducing DAP and sometimes producing fast hyperpolarizing after-potential (HAP) aftershortened AP), and in the presence of 4-AP these activators increase potassium current through unblocked slowpotassium channels (making the development of slow HAP induced by 4-AP more rapid). The increase of slowHAP induced by 4-AP under the influence of potassium-free solution with NO supports the idea that slow HAPis due to activation of slow potassium channels and argues against the notion of removal of block of fast potas-sium channels. All analyzed phenomena of voltage-dependent action of 4-AP in amphibian myelinated nervefibers can be accounted for by the activation of slow potassium current produced by membrane depolarizationand a decrease of the amount of fast potassium channels involved in the membrane repolarization.