Volatile Anesthetic Effects on Sarcoplasmic Reticulum Ca Content and Sarcolemmal Ca Flux in Isolated Rat Cardiac Cell Suspensions
Cardiac cellular Ca metabolism is central to the control of the inotropic state of the heart and is altered in various ways by the volatile anesthetics halothane, enflurane and isoflurane. Specifically, differences among the agents regarding their effect on the uptake and release of Ca from the sarcoplasmic reticulum (SR) have been found, but the nature of such differences is not yet certain. At the sarcolemma, the effects of the anesthetics on the peak Ca current generally are believed to be similar among the three agents, but their impact on other aspects of sarcolemmal Ca transport is less understood. The authors sought to measure the direct action of these agents on SR Ca content and, in the same preparation, to provide a measure of Ca transfer across the sarcolemma during sustained depolarizations.Methods
In stirred suspensions of quiescent rat cardiac cells, the effects were measured of halothane, enflurane, and isoflurane on changes in quin2Ca fluorescence produced by the addition of caffeine (10 mM) and by depolarization with increased extracellular K+. The peak of the fluorescence response to caffeine, which is due to a sudden release of Ca from the SR into the cytoplasm, was used as an index of SR Ca content. Analysis of the fluorescence increase that occurred after increasing extracellular K+ from 5 mM to 30 mM in the presence of caffeine provided a measure of net Ca influx across the sarcolemma during sustained depolarizations.Results
The Ca channel blocker nitrendipine maximally inhibited 77% of the initial net Ca influx during 30 mM K+ depolarization, indicating that most of this influx involves L-type Ca channels. Of the volatile anesthetics, isoflurane (2.6 vol% or 0.57 mM) and enflurane (4.3 vol% or 1.25 mM) inhibited initial net Ca influx during K depolarization significantly more than halothane (1.7 vol% or 0.50 mM), which had no apparent effect. Isoflurane caused no transient change in cytoplasmic Ca concentration and had no effect on the SR Ca content of these quiescent cells. Enflurane (4.3 vol%) caused a significant reduction in SR Ca content.Conclusions
As previously reported, halothane depleted the SR of Ca in quiescent rat cardiac cells, and the present results indicate that enflurane had a similar effect. However, isoflurane did not produce any SR Ca depletion and thus must not significantly alter the balance between SR Ca efflux and uptake in these quiescent cells. The different effects of the three volatile anesthetics on a Ca influx largely carried by L-type Ca channels stand in contrast to the reported findings of similar inhibition of peak L-channel current among the three agents. This result may indicate a differential action (at least in the case of halothane) on peak and steady-state Ca currents.