Phase-dependent properties of the cardiac sarcoplasmic reticulum oscillator in cat right atrium: a mechanism contributing to dysrhythmias induced by Ca2+ overload.
These experiments analyse the phase-dependent properties of spontaneous oscillations of the sarcoplasmic reticulum (SR) induced by Ca2+ overload. Right atrial tissue was loaded with intracellular Ca2+ by exposure to a modified Tyrode solution containing 50% of normal Na+ and 0.5 mM K+. Verapamil (2 microM) was added to block regenerative activity. Intracellular Ca2+ overload elicited spontaneous, rhythmic voltage and tension oscillations that were phase locked 1:1. Voltage and tension oscillations were abolished by exposure to low (0.9 mM) external Ca2+, 1 microM ryanodine, or 10 mM caffeine, indicating that both voltage and tension oscillations resulted from spontaneous oscillations in SR Ca2+ release. Single pulses of nerve-stimulated ACh release elicited phase shifts in both voltage and tension oscillations. Sinusoidal current was used as a periodic stimulus to drive membrane voltage and elicit periodic voltage oscillations. Stimulated voltage oscillations entrained spontaneous tension oscillations 1:1 in a range of frequencies close to the basic spontaneous SR oscillatory cycle length, or 2:1 at frequencies close to one-half the spontaneous SR oscillatory cycle length. Stimulation frequencies between these two regions entrained tension oscillations in predictable fixed coupled ratios (4:3, 3:2) and resulted in Wenckeback-like voltage patterns. Stimulation frequencies between phase-locked regions resulted in complex coupling relationships and irregular voltage patterns. Exposure to 1 microM ryanodine, 0.9 mM external Ca2+, or 10 mM caffeine abolished irregular voltage patterns and tension. We conclude that the SR oscillator exhibits phase-dependent sensitivity to perturbations at the surface membrane. As a result, external perturbations can elicit phase differences between spontaneous SR oscillations and membrane voltage that cause either phase-locked or irregular voltage patterns. These findings identify an intracellular mechanism that may contribute to the development of cardiac dysrhythmias resulting from intracellular Ca2+ overload.
Rubenstein
D S
DS
Department of Physiology, Loyola University of Chicago, Stritch School of Medicine, Maywood, IL 60153.
Zbilut
J P
JP
Webber
C L
CL
Lipsius
S L
SL
D000109:Acetylcholine / Q000378:metabolism; D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002415:Cats; D004558:Electric Stimulation; D005260:Female; D006325:Heart Atria / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D009200:Myocardial Contraction / Q000502:physiology; D010507:Periodicity; D012519:Sarcoplasmic Reticulum / Q000502:physiology*
D015220:Calcium Channels; D000109:Acetylcholine; D002118:Calcium