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Published on: July 16, 2013
Action potential modulation of connexin40 gap junctional conductance
Xianming Lin1, Richard D Veenstra
1Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, New York 13210, USA.
American Journal of Physiology. Heart and Circulatory Physiology
|December 25, 2003
Summary
Connexin40 (Cx40) gap junctions show voltage-dependent changes in conductance during cardiac action potentials. These dynamic changes in Cx40 function correlate with cardiac conduction delays and arrhythmias.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Biophysics
Background:
- Connexin40 (Cx40) is crucial for rapid electrical conduction in the mammalian heart.
- Efficient cardiac electrical activity relies on electrotonic potential transfer between cells via gap junctions.
- Understanding Cx40 channel behavior under physiological conditions is vital for cardiac health.
Purpose of the Study:
- To investigate how transjunctional voltages (Vj) during action potentials modulate Cx40 gap junction conductance.
- To characterize the voltage-gating kinetics of Cx40 channels.
- To explore the role of Cx40 junctional conductance changes in cardiac electrophysiology and arrhythmias.
Main Methods:
- Expressed Cx40 gap junctions in mouse neuro2A (N2A) cells.
- Applied simulated myocardial action potentials as voltage-clamp waveforms.
- Analyzed junctional currents and conductance changes in response to varying transjunctional voltages (Vj).
- Modeled Cx40 time-dependent conductance using inactivation and recovery components.
Main Results:
- Junctional currents mirrored action potential morphology, with a >50% decline from peak to plateau.
- Cx40 gating kinetics showed significant voltage dependence, with decay time constants changing e-fold per 17.6 mV for Vj > +/-40 mV.
- Junctional conductance recovered during repolarization and diastole, linked to rapid decay kinetics and steady-state recovery.
- A temporal correlation was observed between Cx40 inactivation and conduction delay/block, and recovery of conductance with refractoriness.
Conclusions:
- Cx40 gap junction conductance is dynamically regulated by transjunctional voltage during cardiac action potentials.
- The voltage-dependent gating kinetics of Cx40 contribute to phasic changes in junctional conductance.
- These findings suggest a significant role for Cx40 gap junctions in the initiation and propagation of cardiac arrhythmias.
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