title: Doxorubicin alters Ca(2+) transients but fails to change Ca(2+) sensitivity of contractile proteins.
abstract: Doxorubicin produced a transient increase and a subsequent decrease in the amplitude of twitch contraction in myocytes isolated from guinea-pig heart and loaded with fura-2. These changes were associated with an increase and a subsequent decrease, respectively, in the amplitude of Ca(2+) transients (peak minus diastolic Ca(2+) concentrations). Doxorubicin increased the diastolic Ca(2+) concentration with a concomitant shortening of the diastolic myocyte length. The time to peak Ca(2+) transients and the time to peak twitch contraction increased in parallel. Doxorubicin failed to affect the Ca(2+) concentration-contraction curve in skinned fibers obtained from atrial muscle. We conclude that biphasic inotropic effects of doxorubicin result from biphasic changes in Ca(2+) transients, and that doxorubicin fails to alter Ca(2+) sensitivity of contractile proteins. These findings are consistent with the hypothesis that doxorubicin enhances Ca(2+) release and impairs Ca(2+) uptake by the sarcoplasmic reticulum.
authors.affiliation: Department of Veterinary Pharmacology, School of Veterinary Medicine and Animal Sciences, Kitasato University, Higashi 23-bancho, Towada-shi, Aomori 034, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Temma
authors.forename: A
authors.initials: A
authors.lastname: Chugun
authors.forename: T
authors.initials: T
authors.lastname: Akera
authors.forename: H
authors.initials: H
authors.lastname: Kondo
authors.forename: N
authors.initials: N
authors.lastname: Kurebayashi