Different voltage-dependent potassium conductances regulate action potential repolarization and excitability in frog...

Intracellular microelectrode recordings were used to examine the effects of the potassium channel blockers: 4-aminopyridine, a selective blocker of fast potassium conductances gKf1 and gKf2,13 and tetraethylammonium, a blocker of gKf1, gKf2 and the slow conductance gKs,13 on the repetitive activity of large myelinated axons of frog. The blockers were applied intracellularly by diffusional leak of the agents from the recording microelectrode containing either 4-aminopyridine or a mixture of 4-aminopyridine and tetraethylammonium. A decrease in outward rectification, a measure of the block of the potassium conductances, was evident within 5 min of axon impalement. Within 30 min 80% of maximal blockade was observed during prolonged recording sessions (> 1 h). Parallel with the resistance increase, the action potential duration increased (up to 5 ms). This was attributed to the block of gKf2. The excitability regularly increased, manifested as a train of action potentials (a decrease in accommodation) for a maximum of 200 ms (54 +/- 8 vs 111 +/- 22, 4-aminopyridine vs 4-aminopyridine-tetraethylammonium, respectively, n = 8 and 6, P < 0.006). The presence of 4-aminopyridine-tetraethylammonium in the microelectrodes decreased the spike frequency adaptation (the instantaneous action potential frequency per spike interval number) observed in fibres treated with 4-aminopyridine alone (32 +/- 9 vs 7 +/- 1 Hz; 4-aminopyridine vs 4-aminopyridine-tetraethylammonium, n = 8 and 6, P < 0.04). This effect was attributed to block of gKs by the tetraethylammonium.(ABSTRACT TRUNCATED AT 250 WORDS)