CONTRIBUTION OF SARCOPLASMIC RETICULAR CALCIUM TO SMOOTH-MUSCLE CONTRACTILE ACTIVATION - GESTATIONAL DEPENDENCE IN ISOLATED RAT UTERUS

1. The contribution of Ca2+ released from the sarcoplasmic reticulum ( SR) to smooth muscle contractile activation remains poorly understood. By simultaneously monitoring cytosolic [Ca2+] ([Ca2+](i)) and force i n isolated rat uterine smooth muscle, we report the influence of SXR C a2+ release on contractility during conditions (a) of altered SR Ca2homeostasis and (b) where the only source of activating Ca2+ was deriv ed from the SR. 2. In myometria of non-pregnant rats, ryanodine (1-50 mu M), a modulator of calcium-induced calcium release (CICR), had no e ffect on the spontaneous [Ca2+](i) or force transients. However, deple tion of SR Ca2+ by inhibiting the SR Ca2+-ATPase (with cyclopiazonic a cid (CPA), 20 mu M) resulted in an enhancement of spontaneous [Ca2+](i ) and force transients. 3. In myometria of pregnant rats, although rya nodine had no effect in 40% of tissues studied it produced a small but significant enhancement of the integrated spontaneous [Ca2+](i) and f orce transient in 60% of cases. The potentiating effects of CPA were e nhanced in myometria of pregnant rats compared with non-pregnant rats, often resulting in maintained [Ca2+](i) increases and contraction. In zero external Ca2+, agonist-induced SR Ca2+ release resulted in trans ient increases in [Ca2+](i) and force. The magnitude of these agonist- induced [Ca2+](i) and force changes were significantly enhanced in myo metria of pregnant rats. No evidence for agonist-induced Ca2+ independ ent force production was observed. 5. These results indicate that CICR plays little role in SR Ca2+ release from the myometrium, and that th ere are gestational-dependent alterations in the ability of SR Ca2+ mo bilization to contribute to contractile activation. The implications o f these findings for the co-ordination of myometrial [Ca2+](i) signall ing and contractility are discussed.