Effects of halothane on [Ca2+]i transient, SR Ca2+ content, and force in intact rat heart trabeculae

The goal of this study was to test whether the well-known cardiodepressant effect of halothane is caused mainly by depression of the transient increase in intracellular Ca2+ concentration ([Ca2+]i) during a twitch. Intact rat ventricular trabeculae, paced at 0.5 Hz and 30 degrees C with a bathing extracellular Ca2+ concentration ([Ca2+]o) of 2 mM, were used. The [Ca2+]i was monitored with the use of fura 2 injected into the myoplasm. The sarcoplasmic reticulum (SR) Ca2+ content was estimated with the use of rapid cooling (RC)-induced contracture force and Ca2+ release. The relationship of the peak [Ca2+]i transient versus peak twitch force obtained with halothane is intermediate between those obtained with lowered [Ca2+]o and varying doses of 2,3-butanedione monoxime. The data indicate that the negative inotropic action of halothane at low (0.18 mM) dose is mainly achieved by reduction in the Ca2+ sensitivity of the contractile apparatus, whereas, at high dose (0.55 mM), halothane acts both by reducing the [Ca2+]i transient and the Ca2+ sensitivity of the contractile system. At moderate (0.37 mM) dose, the effects were midway between low and high doses. With the use of RC contracture force alone, the reduction of SR Ca2+ content caused by halothane is overestimated.