Phase-dependent properties of the cardiac sarcoplasmic reticulum oscillator in cat right atrium: a mechanism contributing to dysrhythmias induced by Ca2+ overload

• Published in: Experimental physiology Vol. 78; no. 1; pp. 79 - 93
• Main Authors: DS Rubenstein, JP Zbilut, Webber CL, Jr, SL Lipsius
• Format: Journal Article
• Language: English
• Published: Cambridge The Physiological Society 01.01.1993; Cambridge University Press
• Subjects: Acetylcholine - secretion; Action Potentials; Animals; Arrhythmias, Cardiac - etiology; Arrhythmias, Cardiac - physiopathology; Biological and medical sciences; Calcium - metabolism; Calcium Channels - metabolism; Cardiac dysrhythmias; Cardiology. Vascular system; Cats; Electric Stimulation; Female; Heart; Heart Atria - physiopathology; In Vitro Techniques; Male; Medical sciences; Membrane Potentials; Myocardial Contraction - physiology; Periodicity; Sarcoplasmic Reticulum - physiology; Heart; Fissipedia; Carnivora; Spontaneous oscillation; Pathophysiology; Calcium; Arrhythmia; Free ion; Phase synchronization; Cardiovascular disease; Biological rhythm; Vertebrata; Mammalia; Overload; Sarcoplasmic reticulum; Animal; Cat; Desynchronization; Membrane potential; Right atrium
• ISSN: 0958-0670; 1469-445X
• DOI: 10.1113/expphysiol.1993.sp003672

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.