The effect of internal and external 4‐aminopyridine on the potassium currents in intracellularly perfused squid giant axons

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Abstract
The effect of 4-aminopyridine (4-AP) on the K outward and inward currents in perfused giant axons of Loligo forbesi was studied with the voltage-clamp technique. Small internal or external 4-AP concentrations (10-100 .mu.M) considerably delay the rise of the K outward current. Repetitive pulsing with a pulse interval of 0.1-5 s leads to a faster rise of the K current; in 10 .mu.M 4-AP a small effect is visible even with a pulse interval of 60 s. The phenomenon was studied quantitatively by using a pre-pulse of varying height and duration, followed after 5 s by a constant test pulse. The effect of changing the holding potential was investigated. The effect of repetitive pulsing disappears in higher 4-AP concentrations; 1-10 mM 4-AP markedly reduce the size of the K outward current; the blocking effect is less pronounced for large depolarizing pulses than for small. In K-rich sea water 4-AP reduces the K outward current and the K inward current; the blocking effect on the K outward current is smaller than in K-free sea water. The K outward current in fibers treated with 10 .mu.M 4-AP and immersed in K-rich sea water is increased and accelerated by repetitive depolarizing pulses. The effect of repetitive pulsing is not dependent on the size of the K outward current (which can be increased by removing K inactivation). The effect of repetitive pulsing and the voltage dependence of the 4-AP block can be explained by the hypothesis that 4-AP molecules are displaced from their blocking sites during the pulse and slowly rebound afterwards. Removal of the 4-AP by a depolarizing pulse seems to be a direct effect of the potential during the pulse and not related to K current.