Calcium- and sodium-dependent modulation of stretch-induced arrhythmias in isolated canine ventricles.
Gadolinium-sensitive stretch-activated channels have been implicated in the process of mechanotransduction signaling of ventricular myocardium. Such channels nonspecifically transport Na+ and Ca2+ in the inward direction. We tested the hypothesis that Na+ and Ca2+ influx are important in the genesis of stretch-induced arrhythmias (SIAs) in an isolated, blood-perfused canine ventricle. To elicit SIAs, left ventricular volume was transiently increased in early diastole using a computerized 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 decrease in the volume change required to precipitate an arrhythmia 50% of the time (delta V50) from 19.5 +/- 2.7 to 15.2 +/- 1.9 ml (P < 0.05). When the perfusate Na+ concentration was decreased from 150 to 90 mM in seven ventricles, delta V50 greatly increased (31.1 +/- 14.4 vs. 17.7 +/- 5.3 ml, P < 0.05), and SID amplitude decreased by 47% (P = 0.002). 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 (and probably that of Ca2+) modulates the amplitude of SIDs, which, in turn, initiate SIAs. These data provide initial evidence that Na+ and Ca2+ help mediate the mechanotransduction processes that underly the genesis of SIAs.
Hansen
D E
DE
Division of Cardiology, Vanderbilt University Medical School, Nashville, Tennessee 37232, USA.
Stacy
G P
GP
Taylor
L K
LK
Jobe
R L
RL
Wang
Z
Z
Denton
P K
PK
Alexander
J
J
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology*; D002118:Calcium / Q000494:pharmacology*; D004285:Dogs; D004594:Electrophysiology; D006439:Hemodynamics / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000502:physiology*; D009994:Osmolar Concentration; D051381:Rats; D012964:Sodium / Q000494:pharmacology*; D016276:Ventricular Function
D008012:Lidocaine; D012964:Sodium; D002118:Calcium