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Am J Physiol Heart Circ Physiol 286: H1726-H1735, 2004. First published December 23, 2003; doi:10.1152/ajpheart.00943.2003
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Action potential modulation of connexin40 gap junctional conductance

Xianming Lin and Richard D. Veenstra

Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, New York 13210

Submitted 2 October 2003 ; accepted in final form 19 December 2003

Connexin40 (Cx40) is abundantly expressed in the atrial myocardium, ventricular conduction system, and vascular endothelial and smooth muscle cells of the mammalian cardiovascular system. Rapid conduction through cardiac tissues depends on electrotonic transfer of the action potential between neighboring cells. To determine whether transjunctional voltages (Vj) elicited by an action potential can modulate conductance of Cx40 gap junctions, simulated myocardial action potentials were applied as voltage-clamp waveforms to Cx40 gap junctions expressed in mouse neuro2A (N2A) cells. Junctional currents resembled the action potential morphology but declined by >50% from peak to near-constant plateau values. Kinetics of Cx40 voltage gating were examined at peak voltages >=100 mV, and decay time constants changed e-fold per 17.6 mV for Vj > ±40 mV. Junctional conductance recovered during phase 3 repolarization and early diastole to initial values. These phasic changes in junctional conductance were due to rapid decay kinetics, increasing to tens of milliseconds at peak Vj of 130 mV, and the increase in the steady-state conductance curve as Vj returned toward 0 mV. Time-dependent conductance curves for Cx40 were modeled with one inactivation and two recovery Vj-dependent components. There was a temporal correlation between development of conduction delay or block and the inactivation phase of junctional conductance. Likewise, recovery of junctional conductance was coincident with recovery from refractoriness, suggesting that gap junctions may play a role in the genesis and propagation of cardiac arrhythmias.

gap junction; ion channel; electrophysiology; transjuctional voltage



Address for reprint requests and other correspondence: R. D. Veenstra, Dept. of Pharmacology, SUNY Upstate Medical Univ., 750 E. Adams St., Syracuse, NY 13210 (E-mail: veenstrr{at}upstate.edu).




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X. Lin, J. Gemel, E. C. Beyer, and R. D. Veenstra
Dynamic model for ventricular junctional conductance during the cardiac action potential
Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1113 - H1123.
[Abstract] [Full Text] [PDF]




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