The effect of yohimbine on sodium and gating currents in frog Ranvier node membrane.

The indolalkylamine alkaloid yohimbine induced two phenomenologically-different types of sodium current (INa) inhibition in the voltage-clamped frog node of Ranvier, a tonic and a phasic ('use-dependent') block. The latter developed during a repetitive membrane stimulation with short (5 ms) depolarizing pulses at frequencies at 1 to 10 Hz. Unlike repetitive pulsing, a single-long lasting (1 s) depolarizing step did not produce a phasic block. Turning on a hyperpolarizing prepulse (50 ms to E = -123 mV) immediately before each test pulse produced a gradual unblocking of Na channels, while a depolarizing prepulse (to -86 mV) enhanced the phasic block. Yohimbine blocked the outward INa much more strongly than the inward ones. Reduction of external Na+ ions concentration from 112 to 55 mM caused a shift in the voltage-department of yohimbine block to more negative voltages, which coincided with the shift of INa reversal potential. Sodium current inhibition produced by yohimbine was accompanied by partial depression of the intramembrane charge movements ('ON-response'). Modification of Na channels by batrachotoxin made the Na channels resistant to both tonic and phasic blocking action of yohimbine. The features of the yohimbine-induced block suggest an interaction of the drug with open Na channels. The current-dependence of yohimbine block indicates an electrostatic interaction between Na+ ion and charged (protonated) form of yohimbine within the channel lumen and suggests the localization of the receptor at the inner mouth of the channel. Binding of yohimbine to the channel receptor promotes the inactivation of this channel. Comparison of the effects of yohimbine on NA and gating currents with those of local anesthetics leads us to suggest that these drugs share a common receptor.