title: Halothane alters control of intracellular Ca2+ mobilization in single rat ventricular myocytes.
abstract: In an attempt to understand the cellular mechanisms underlying volatile anesthetic-induced myocardial depression, halothane-induced negative inotropy was investigated in an animal model through continuous monitoring of intracellular Ca2+ concentration [( Ca2+]i) in rat ventricular myocytes loaded with fura-2. Single cells were stimulated with 15 mM caffeine or 15 mM extracellular K+ (K+O) or were paced by extracellular glass suction pipette electrode. With each stimulus modality, halothane (0.6-1.5%) caused a significant (P less than 0.05) and dose-dependent depression of the Ca2+ transient. Caffeine and electrically stimulated Ca2+ transients were reduced, in 1.5% halothane, to 35 +/- 14 and 42 +/- 8% of control, respectively. Resting or basal [Ca2+]i was unaffected by halothane. Halothane did not elicit spontaneous Ca2+ transients in these cells. Single cells stimulated by trains of electrical stimuli at 1.0, 1.5, and 2.0 Hz showed a change in [Ca2+]i from prestimulus levels to a stimulated baseline steady state that appeared to increase with stimulus frequency. Halothane at 0.7% increased the change in resting to stimulated baseline [Ca2+]i and depressed net transients (P less than 0.05) at 1.0 and 1.5 Hz. In contrast, 0.1 microM ryanodine depressed the Ca2+ transients in myocytes stimulated by trains of stimuli, but did not potentiate the change in stimulated baseline [Ca2+]i at any pacing rate. The results are consistent with the hypothesis that halothane reduces Ca2+i availability by causing a net loss of Ca2+ from the sarcoplasmic reticulum. The results from experiments using onset of pacing to induce a sudden increase in Ca2+i load in previously quiescent myocytes suggest that halothane may act to limit sarcoplasmic reticulum and/or sarcolemmal uptake/extrusion mechanisms, as compared to ryanodine, which depletes sarcoplasmic reticulum Ca2+ stores without affecting reuptake and extrusion.
authors.affiliation: Department of Anesthesiology, University of Michigan Medical School, Ann Arbor.
authors.forename: D W
authors.initials: DW
authors.lastname: Wilde
authors.forename: P R
authors.initials: PR
authors.lastname: Knight
authors.forename: N
authors.initials: N
authors.lastname: Sheth
authors.forename: B A
authors.initials: BA
authors.lastname: Williams
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004558:Electric Stimulation; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D006352:Heart Ventricles / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002110:Caffeine; D011188:Potassium; D002118:Calcium; D006221:Halothane