VOLATILE ANESTHETIC EFFECTS ON SARCOPLASMIC-RETICULUM CA CONTENT AND SARCOLEMMAL CA FLUX IN ISOLATED RAT CARDIAC CELL-SUSPENSIONS

Background: Cardiac cellular Ca metabolism is central to the control o f the inotropic state of the heart and is altered in various ways by t he volatile anesthetics halothane, enflurane and isoflurane. Specifica lly, differences among the agents regarding their effect on the uptake and release of Ca from the sarcoplasmic reticulum (SR) have been foun d, but the nature of such differences is not yet certain. At the sarco lemma, the effects of the anesthetics on the peak Ca current generally are believed to be similar among the three agents, but their impact o n other aspects of sarcolemmal Ca transport is less understood. The au thors sought to measure the direct action of these agents on SR Ca con tent and, in the same preparation, to provide a measure of Ca transfer across the sarcolemma during sustained depolarizations. Methods: In s tirred suspensions of quiescent rat cardiac cells, the effects were me asured of halothane, eflurane, and isoflurane an changes in quin2Ca fl uorescence produced by the addition of caffeine (10 mM) and by depolar ization 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 extracell ular K+ from 5 mM to 30 mw in the presence of caffeine provided a meas ure of net Ca influx across the sarcolemma during sustained depolariza tions. Results: The Ca channel blocker nitrendipine maximally inhibite d 77% of the initial net Ca influx during 30 mM K+ depolarization, ind icating that most of this influx involves L-type Ca channels. Of the v olatile 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 depolariz ation significantly more than halothane (1.7 vol% or 0.50 mM), which h ad no apparent effect. Isoflurane caused no transient change in cytopl asmic 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 deple ted the SR of Ca in quiescent rat cardiac cells, and the present resul ts indicate that enflurane had a similar effect. However, isoflurane d id not produce any SR Ca depletion and thus must not significantly alt er the balance between SR Ca efflux and uptake in these quiescent cell s. The different effects of the three volatile anesthetics on a Ca inf lux largely carried by L-type Ca channels stand in contrast to the rep orted findings of similar inhibition of peak I-channel current among t he three agents. This result may indicate a differential action (at le ast in the case of halothane) on peak and steady-state Ca currents.