Dynamics of aminopyridine block of potassium channels in squid axon membrane.

Open Access
Publisher Website
Google Scholar
Abstract
Aminopyridines (2-AP, 3-AP, and 4-AP) selectively blocked K+ channels of squid [Loligo pealei] axon membranes in a manner dependent upon the membrane potential and the duration and frequency of voltage clamp pulses. They were effective when applied to either the internal or the external membrane surface. The steady-state block of K+ channels by aminopyridines was more complete for low depolarizations, and was gradually relieved at higher depolarizations. The K+ current in the presence of aminopyridines rose more slowly than in control, the change being more conspicuous in 3-AP and 4-AP than in 2-AP. Repetitive pulsing relieved the block in a manner dependent upon the duration and interval of pulses. The recovery from block during a given test pulse was enhanced by increasing the duration of a conditioning depolarizing prepulse. The time constant for this recovery was in the range of 10-20 ms in 3-AP and 4-AP, and shorter in 2-AP. Twin pulse experiments with variable pulse intervals revealed that the time course for re-establishment of block was much slower in 3-AP and 4-AP than in 2-AP. 2-AP seemed to interact with the K+ channel more rapidly than 3-AP and 4-AP. The more rapid interaction of 2-AP with K+ channels is reflected in the kinetics of K+ current which was faster than that observed in 3-AP or 4-AP, and in the pattern of frequency-dependent block which was different from that in 3-AP or 4-AP. The experimental observations were not satisfactorily described by alterations of Hodgkin-Huxley n-type gating units. The data seemed consistent with a simple binding scheme incorporating no changes in gating kinetics which conceived of aminopyridine molecules binding to closed K+ channels and being released from open channels in a voltage-dependent manner.