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Biophysical Journal 55: 1261-1266 (1989)
© 1989 the Biophysical Society

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Use-dependent block of single sodium channels by lidocaine in guinea pig ventricular myocytes.

T V McDonald, K R Courtney and W T Clusin

Falk Cardiovascular Research Center, Stanford University School of Medicine, California 94305.

ABSTRACT

Single sodium channel openings have been recorded from cell-attached patches of isolated guinea pig ventricular myocytes. A paired pulse protocol was used to test the hypothesis that channel openings are required for lidocaine block. While the averaged ensemble current during the test pulse was much reduced, there was no correlation between the appearance of channel openings during the conditioning pulse and the subsequent test pulse. Analysis of single channel records demonstrated that the unit conductance of open channels was not changed by lidocaine. The block of ensemble INa was explained by roughly equal reductions in number of open channel events, and in the average duration of opening for each event. These results suggest that lidocaine binding to Na+ channels is dependent upon voltage, but may occur before channel opening. A lidocaine-modified channel can still open, but will be less likely to remain open than a drug-free channel. These results are consistent with block of a pre-open state of the channel.




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P. B. Bennett, C. Valenzuela, L.-Q. Chen, and R. G. Kallen
On the Molecular Nature of the Lidocaine Receptor of Cardiac Na+ Channels : Modification of Block by Alterations in the {alpha}-Subunit III-IV Interdomain
Circ. Res., September 1, 1995; 77(3): 584 - 592.
[Abstract] [Full Text]


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Copyright © 1989 by the Biophysical Society.