Effects of Volatile Anesthetics on the Intracellular Ca2+ Concentration in Cardiac Muscle Cells
The myocardial depressant effects of the three halogenated volatile anesthetics, halothane, enflurane and isoflurane, have been well documented clinically and experimentally.1–4 In recent years multiple mechanisms of action of these agents have been demonstrated. The results of a number of studies have pointed to anesthetic effects on transmembrane signalling in a variety of cell types as a central facet of anesthetic action (for brief review see Maze5). Many efforts have been made to elucidate the mechanisms by which these agents alter excitation-contraction coupling in the heart to produce negative inotropy. Halothane, for example, has been observed to depress myocardial contractility4 through depletion of the sarcoplasmic reticulum (SR) stores of calcium (Ca2+).6–9 The evidence suggests that the negative inotropic effect of halothane is mediated by enhancement of Ca2+ efflux through SR Ca2+ release channels.10 Halothane’s effects to limit availability of Ca2+ for contraction do not appear restricted to actions on SR Ca2+ release, however. Direct effects of halothane on myocardial Ca2+ channels have also been proposed,11 although it remains unclear whether this is a direct effect on the L-type Ca2+ channels, or instead the indirect effect of a change in some intracellular mediator. Halothane may also alter Ca2+ uptake by the myocardial SR12,13 and have effects on mitochondrial Ca2+ metabolism and storage. These various putative mechanisms may act alone or in combination to limit Ca2+ availability for contraction in the heart.
KeywordsSarcoplasmic Reticulum Volatile Anesthetic Anesthetic Action Transient Amplitude Cardiac Sarcoplasmic Reticulum
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