CALCIUM-DEPENDENT AND SODIUM-DEPENDENT MODULATION OF STRETCH-INDUCED ARRHYTHMIAS IN ISOLATED CANINE VENTRICLES

Gadolinium-sensitive stretch-activated channels have been implicated i n the process of mechanotransduction signaling of ventricular myocardi um. Such channels nonspecifically transport Na+ and Ca2+ in the inward direction. We tested the hypothesis that Na+ and Ca2+ influx are impo rtant in the genesis of stretch-induced arrhythmias (SIAs) in an isola ted, blood-perfused canine ventricle. To elicit SIAs, left ventricular volume was transiently increased in early diastole using a computeriz ed servo-pump system. Monophasic action potential recordings revealed stretch-induced depolarizations (SIDs) that preceded the arrhythmias. In five ventricles, raising the perfusate Ca2+ concentration from 1 to 3 mM increased ventricular sensitivity to SIAs, manifested by a decre ase in the volume change required to precipitate an arrhythmia 50% of the time (Delta V-50) from 19.5 +/- 2.7 to 15.2 +/- 1.9 ml (P < 0.05). When the perusate Na+ concentration was decreased from 150 to 90 mM i n seven ventricles, Delta V-50 greatly increased (31.1 +/- 14.4 vs. 17 .7 +/- 5.3 ml, P < 0.05), and SID amplitude decreased by 47% (P = 0.00 2). The suppression of SIAs with low extracellular Na+ is unlikely to be mediated by voltage-gated Na+ channels because lidocaine (5 mg/dl) did not alter SID amplitude. Thus the transsarcolemmal Na+ gradient (a nd probably that of Ca2+) modulates the amplitude of SIDs, which, in t urn, initiate SIAs. These data provide initial evidence that Na+ and C a2+ help mediate the mechanotransduction processes that underly the ge nesis of SIAs.