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Phase‐dependent properties of the cardiac sarcoplasmic reticulum oscillator in cat right atrium: a mechanism contributing to dysrhythmias induced by Ca2+ overload
Author(s) -
Rubenstein DS,
Zbilut JP,
Lipsius SL
Publication year - 1993
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.1993.sp003672
Subject(s) - ryanodine receptor , biophysics , chemistry , caffeine , purkinje fibers , endoplasmic reticulum , medicine , electrophysiology , nuclear magnetic resonance , physics , biology , biochemistry
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.