Biophysical Journal 59: 150-161 (1991)
© 1991 the Biophysical Society

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Balser, J R Articles by Bennett, P B Search for Related Content PubMed PubMed Citation Articles by Balser, J R Articles by Bennett, P B

Single inward rectifier potassium channels in guinea pig ventricular myocytes. Effects of quinidine.

Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.

ABSTRACT

The effects of quinidine on single inward rectifier K channels were investigated in cell-attached patches with 4.5 mM pipette potassium concentrations. Under these conditions, the single-channel slope conductance of the predominant conductance level of the inward rectifier channels was 3.9 +/- 0.3 pS at membrane potentials between -75 and -150 mV. Quinidine reversibly decreased the likelihood of channel opening to the main conductance level without reducing the single-channel conductance, and also reduced the probability of channel opening to subconducting levels. Quinidine had no significant effects on the channel open times, and the inhibition of channel opening was only slightly voltage dependent over the range of membrane potentials investigated. Quinidine induced a complete cessation of channel openings for brief periods (up to 2 min), suggesting that quinidine promoted occupancy of a state from which opening was less likely. Occasional long periods (up to an hour) with an absence of channel activity were also observed but quinidine did not appear to promote this behavior. The data suggest that quinidine decreases the ability of the channel to enter both main and subconducting states. By binding to a particular closed conformation of the channel, quinidine could reduce the likelihood of channel opening. The main features of these observations could be accounted for using the three-state kinetic model proposed by Sakmann, B. and G. Trube (1984b. J. Physiol. [Lond.]. 347:659-683.) with quinidine binding to the middle closed state.

This article has been cited by other articles:

				H. Zhang, B. Zhu, J.-A. Yao, and G.-N. Tseng Differential Effects of S6 Mutations on Binding of Quinidine and 4-Aminopyridine to Rat Isoform of Kv1.4: Common Site but Different Factors in Determining Blockers' Binding Affinity J. Pharmacol. Exp. Ther., October 1, 1998; 287(1): 332 - 343. [Abstract] [Full Text]

				H. Furushima, S. Niwano, M. Chinushi, K. Ohhira, A. Abe, and Y. Aizawa Relation between bradycardia dependent long QT syndrome and QT prolongation by disopyramide in humans Heart, January 1, 1998; 79(1): 56 - 58. [Abstract] [Full Text] [PDF]

				A. M. Choy, C. C. Lang, D. M. Chomsky, G. H. Rayos, J. R. Wilson, and D. M. Roden Normalization of Acquired QT Prolongation in Humans by Intravenous Potassium Circulation, October 7, 1997; 96(7): 2149 - 2154. [Abstract] [Full Text]

				T. Yang and D. M. Roden Extracellular Potassium Modulation of Drug Block of IKr : Implications for Torsade de Pointes and Reverse Use-Dependence Circulation, February 1, 1996; 93(3): 407 - 411. [Abstract] [Full Text]

				H. J. Duff, Z.-P. Feng, and R. S. Sheldon High- and Low-Affinity Sites for [3H]Dofetilide Binding to Guinea Pig Myocytes Circ. Res., October 1, 1995; 77(4): 718 - 725. [Abstract] [Full Text]

				G. X. Liu and J. Daut 'Sleepy' inward rectifier channels in guinea-pig cardiomyocytes are activated only during strong hyperpolarization J. Physiol., March 15, 2002; 539(3): 755 - 765. [Abstract] [Full Text] [PDF]