Dynamic model for ventricular junctional conductance during the cardiac action potential.
The ventricular action potential was applied to paired neonatal murine ventricular myocytes in the dual whole cell configuration. During peak action potential voltages >100 mV, junctional conductance (g(j)) declined by 50%. This transjunctional voltage (V(j))-dependent inactivation exhibited two time constants that became progressively faster with increasing V(j). G(j) returned to initial peak values during action potential repolarization and even exceeded peak g(j) values during the final 5% of repolarization. This facilitation of g(j) was observed <30 mV during linearly decreasing V(j) ramps. The same behavior was observed in ensemble averages of individual gap junction channels with unitary conductances of 100 pS or lower. Immunohistochemical fluorescent micrographs and immunoblots detect prominent amounts of connexin (Cx)43 and lesser amounts of Cx40 and Cx45 proteins in cultured ventricular myocytes. The time dependence of the g(j) curves and channel conductances are consistent with the properties of predominantly homomeric Cx43 gap junction channels. A mathematical model depicting two inactivation and two recovery phases accurately predicts the ventricular g(j) curves at different rates of stimulation and repolarization. Functional differences are apparent between ventricular myocytes and Cx43-transfected N2a cell gap junctions that may result from posttranslational modification. These observations suggest that gap junctions may play a role in the development of conduction block and the genesis and propagation of triggered arrhythmias under conditions of slowed conduction (<10 cm/s).
Lin
Xianming
X
Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, New York 13210, USA.
Gemel
Joanna
J
Beyer
Eric C
EC
Veenstra
Richard D
RD
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000378:metabolism; D017629:Gap Junctions / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D016276:Ventricular Function
D018031:Connexin 43; D017630:Connexins; C082920:connexin 45