Aminopyridine block of potassium channels in mouse neuroblastoma cells

JK Hirsh and FN Quandt

Multiple Sclerosis Center, Rush University, Chicago, Illinois.

Although 4-aminopyridine (4-AP) is known to block a variety of voltage- dependent K channels, details as to the site of action and the mechanism of block are known for relatively few. Single channel analysis has not been extensively used to answer these questions. The actions of 4-AP on whole cell K currents and single voltage-dependent K channels that exhibit fast activation and inactivation were therefore examined in N1E-115 neuroblastoma cells. The concentration for half block (K0.5) of the whole cell K current for externally applied compounds was found to be 56 microns for 4-AP and 0.3 mM for 3,4- diaminopyridine. 4-AP slowed the rate of development of outward K current, and the rate of decay after repolarization. These effects were consistent with the idea that 4-AP preferentially blocked a type of K channel generating a transient current. Block of this component of current was time- and use-dependent. 4-AP blocked the channel responsible for the transient outward current by decreasing the probability of an open channel in inside-out patches. 4-AP reduced the open time, indicating that 4-AP can interact with the open channel. The first latency to opening was also increased. 4-Aminopyridine methiodide (4-APMI), a permanently charged derivative, blocked the whole cell current with a K0.5 = 0.19 mM. Block by 4-APMI was found to be by a different mechanism at a different site compared to 4-AP.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 267, Issue 2, pp. 604-611, 11/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics

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