DIFFERENT VOLTAGE-DEPENDENT POTASSIUM CONDUCTANCES REGULATE ACTION-POTENTIAL REPOLARIZATION AND EXCITABILITY IN FROG MYELINATED AXON

Intracellular microelectrode recordings were used to examine the effec ts of the potassium channel blockers: 4-aminopyridine, a selective blo cker of fast potassium conductances of g(Kf1) and g(Kf2),(13) and tetr aethylammonium, a blocker of g(Kf1), g(Kf2) and the slow conductance g (Ks),(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-aminopyr idine or a mixture of 4-aminopyridine and tetraethylammonium. A decrea se in outward rectification, a measure of the block of the potassium c onductances, was evident within 5 min of axon impalement. Within 30 mi n 80% of maximal blockade was observed during prolonged recording sess ions (> 1 h). Parallel with the resistance increase, the action potent ial duration increased (up to 5 ms). This was attributed to the block of g(Kf2). The excitability regularly increased, manifested as a train of action potentials (a decrease in accommodation) for a maximum of 2 00 ms (54 +/- 8 vs 111 +/- 22, 4-aminopyridine vs 4-aminopyridine-tetr aethylammonium, respectively, n = 8 and 6, P < 0.006). The presence of 4-aminopyridine-tetraethylammonium in the microelectrodes decreased t he spike frequency adaptation (the instantaneous action potential freq uency per spike interval number) observed in fibres treated with 4-ami nopyridine alone (32 +/- 9 vs 7 +/- 1 Hz; 4-aminopyridine vs 4-aminopy ridine-tetraethylammonium, n = 8 and 6, P < 0.04). This effect was att ributed to block of g(Ks) by the tetraethylammonium. These results sug gest that the two aspects of repetitive activity in myelinated axons a re regulated by different potassium conductances: g(Kf2) modulates the early phase of accommodation and action potential repolarization, whe reas g(Ks) regulates the late phase of accommodation and the spike fre quency adaptation.