Block of sodium current in myelinated nerve fibre with enkephalins

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The effects of leu- and met-enkephalin were investigated on the node of Ranvier of isolated nerve fibres of frog under current and voltage clamp conditions. When added to the external solution, enkephalins (1–5 mM) caused a slight decrease in peak Na + and steady state K + currents. The action potential was not significantly affected. When added to the internal medium (by diffusion from the two cut ends of the fibre), enkephalins (<5 mM) drastically reduced the peak Na + current without significantly affecting the steady state K + current. The block of Na + current was greatly accelerated and enhanced by repetitive depolarizations. The sodium current slowly recovered after the end of pulsing. The extent of the block and rate of accumulation increased with increasing magnitude and frequency of the depolarizing pulses. Internal applications of enkephalins induced a blockade of the action potential when the fibre was stimulated at frequencies above 0.1 Hz. The results suggest that during depolarizations, enkephalin molecules plug the inner end of Na + channels or immobilize the channel gates leaving the channels in a closed configuration, and remain in or near the pores for a long time after the end of depolarizations. Possible physiological significance and molecular mode of action of enkephalins on myelinated nerve fibres are discussed.