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

Abstract Intracellular microelectrode recordings were used to examine the effects of the potassium channel blockers: 4-aminopyridine, a selective blocker of fast potassium conductances g Kf1 and g Kf2 , 13 and tetraethylammonium, 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-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 g Kf2 . The excitability regularly increased, manifested as a train of action potentials (a decrease in accomodation) for a maximum of 200 ms (54 ± 8 vs 111 ± 22, 4-aminopyridine vs 4-aminopyridine-tetraethylammonium, respectively, n = 8 and 6, P ). 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 ). This effect was attributed to block of g Ks by the tetraethylammonium. These results suggest that the two aspects of repetitive activity in myelinated axons are regulated by different potassium conductances: g Kf2 modulates the early phase of accomodation and action potential repolarization, whereas g Ks regulates the late phase of accomodation and the spike frequency adaptation.