BLOCK OF POTASSIUM CHANNELS OF NODAL MEMBRANE BY 4-AMINOPYRIDINE AND ITS PARTIAL REMOVAL ON DEPOLARIZATION

Voltage clamp experiments were done on single myelinated nerve fibers of the frog, Rana esculenta. 4-Aminopyridine (4-AP) (53 .mu.M) reduced IK [K+ current] to about 1/5 if tested with infrequent (1/min) and short (10 ms) depolarizing pulses; the onset time constant under these circumstances was about 160 s (14-15.degree. C). After prolonged treatment the effect was virtually irreversible. At equilibrium with 4-AP, increasing the frequency of short pulses removed part of the block, the block removal accelerating with increasing pulse duration and frequency. In 53 .mu.M 4-AP unblocking of K+ channels during long (0.8 s) depolarizing pulses proceeded with a time constant, .tau.r, of about 0.2 s. Restoration of block at the resting potential proceeded with a much larger time constant, .**GRAPHIC**. of about 1 min. The stationary fraction, r.infin., of K+ channels conducting in 53 .mu.M 4-AP was 0.66, 0.41 and 0.24 at V = 120, 50 and 0 mV, respectively. In a series of experiments with [4-AP] varying between 13.3-848 .mu.M, .tau.r decreased from 0.25 to 0.10 s (V = 130 mV, about 17.degree. C) while r.infin. followed the empirical relation 1/r.infin. = 1 + ct + cv exp(-0.77 EF/RT) with E = V - 70mV. The terms ct and cv were dimensionless quantities that increased with [4-AP] and reflected the voltage-independent and voltage-dependent component, respectively, of block. Block of K+ channels and partial removal were also observed with inward IK at raised [K+]0. Removal proceeded on depolarization even if IK was additionally but temporarily suppressed by tetraethylammonium. Hence neither direction nor amplitude of IK but only the pulse potential seems to determine the extent of block for a given [4-AP].