Molecular mechanisms of K+ channel blockade: 4-Aminopyridine interaction with a cloned cardiac transient K+ (Kv1.4) channel

R. L. Rasmusson, Y. Zhang, D. L. Campbell, M. B. Comer, R. C. Castellino, S. Liu, M. J. Morales, H. C. Strauss, H. Fozzard, E. Marban, Y. Rudy, M. Lab

Research output: Contribution to journalArticlepeer-review

Abstract

We studied the blocking effects of 4-aminopyridine (4-AP) on a Kv1.4 K+ channel. A permanently charged 4-AP derivative only produced block when applied intracellularly. 4-AP block accumulated from pulse to pulse indicating trapping of 4-AP in deactivated channels. For long trains of depolarizing pulses, 4-AP block increased with decreasing pulse duration. This increase took many pulses (>10) to accumulate and was relieved by two to three subsequent pulses of 500 msec duration. We conclude that the time- and voltage-dependence of 4-AP block can not be accounted for solely by either simple pure open channel or pure closed channel blocking schemes. We propose that the data can be explained by a model in which 4-AP binding is most stable when the channel has a symmetric arrangement in the binding regions.

Original languageEnglish (US)
Pages (from-to)11-22
Number of pages12
JournalAdvances in Experimental Medicine and Biology
Volume382
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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