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Mechanical Stimulation-induced Calcium Wave Propagation in Cell Monolayers: The Example of Bovine Corneal Endothelial Cells
Published on: July 16, 2013
Enhancement of ventricular gap-junction coupling by rotigaptide
Xianming Lin1, Christian Zemlin, James K Hennan
1Department of Pharmacology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.
Cardiovascular Research
|April 24, 2008
Summary
Rotigaptide enhances cardiac gap-junction conductance, improving electrical signal propagation. This mechanism explains its anti-arrhythmic effects by normalizing myocardial communication and preventing re-entrant circuits.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Pharmacology
Background:
- Cardiac arrhythmias are often caused by impaired myocardial gap-junction communication.
- Rotigaptide is a potential anti-arrhythmic drug proposed to improve gap-junction function.
Purpose of the Study:
- To directly investigate the effects of rotigaptide on gap-junctional currents in cardiomyocytes.
- To elucidate the mechanisms underlying rotigaptide's anti-arrhythmic properties.
Main Methods:
- Neonatal murine ventricular cardiomyocytes were cultured and subjected to dual whole-cell patch-clamp.
- Gap-junctional currents (I(j)) and voltage (V(j)) were measured.
- Rotigaptide was applied acutely or chronically at various concentrations.
Main Results:
- Therapeutic concentrations (35-100 nM) of rotigaptide increased resting gap-junction conductance (g(j)) and normalized steady-state minimum g(j) (G(min)).
- Higher concentrations showed diminishing responses, correlating with therapeutic efficacy.
- Rotigaptide slowed inactivation kinetics without altering voltage dependence, and computer simulations confirmed its ability to reverse conduction slowing.
Conclusions:
- Rotigaptide increases resting gap-junction conductance and reduces steady-state inactivation in a concentration-dependent manner.
- These effects suggest rotigaptide's efficacy in treating re-entrant arrhythmias by improving conduction in partially uncoupled myocardium.
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