Conduction slowing by the gap junctional uncoupler carbenoxolone
Open Access
- 1 November 2003
- journal article
- Published by Oxford University Press (OUP) in Cardiovascular Research
- Vol. 60 (2) , 288-297
- https://doi.org/10.1016/j.cardiores.2003.07.004
Abstract
Background: Cellular electrical coupling is essential for normal propagation of the cardiac action potential, whereas reduced electrical coupling is associated with arrhythmias. Known cellular uncoupling agents have severe side effects on membrane ionic currents. We investigated the effect of carbenoxolone on cellular electrical coupling, membrane ionic currents, and atrial and ventricular conduction. Methods and Results: In isolated rabbit left ventricular and right atrial myocytes, carbenoxolone (50 μmol/l) had no effect on action potential characteristics. Calcium, potassium, and sodium currents remained unchanged. Dual current clamp experiments on poorly coupled cell pairs revealed a 21±3% decrease in coupling conductance by carbenoxolone (mean±S.E.M., n = 4, p3 (mean±SD, n = 32, pn = 5, both pn = 8, both pConclusions: Carbenoxolone-induced uncoupling causes atrial and ventricular conduction slowing without affecting cardiac membrane currents. Activation delay is larger in poorly coupled cells.Keywords
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