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...
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Published in | Experimental physiology Vol. 78; no. 1; pp. 79 - 93 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Cambridge
The Physiological Society
01.01.1993
Cambridge University Press |
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Abstract | 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. |
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AbstractList | 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. 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. |
Author | DS Rubenstein JP Zbilut SL Lipsius Webber CL, Jr |
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Keywords | 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 |
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Snippet | These experiments analyse the phase-dependent properties of spontaneous oscillations of the sarcoplasmic reticulum (SR) induced
by Ca2+ overload. Right atrial... These experiments analyse the phase‐dependent properties of spontaneous oscillations of the sarcoplasmic reticulum (SR) induced by Ca2+ overload. Right atrial... These experiments analyse the phase-dependent properties of spontaneous oscillations of the sarcoplasmic reticulum (SR) induced by Ca2+ overload. Right atrial... |
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SubjectTerms | 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 |
Title | Phase-dependent properties of the cardiac sarcoplasmic reticulum oscillator in cat right atrium: a mechanism contributing to dysrhythmias induced by Ca2+ overload |
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