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 in isolated rat uterine smooth muscle, we report the influence of SR Ca2+ release on contractility during conditions (a) of altered SR Ca2+ homeostasis and (b) where the only source of activating Ca2+ was derived from the SR. 2. In myometria of non-pregnant rats, ryanodine (1-50 microM), a modulator of calcium-induced calcium release (CICR), had no effect on the spontaneous [Ca2+]i or force transients. However, depletion of SR Ca2+ by inhibiting the SR Ca2+-ATPase (with cyclopiazonic acid (CPA), 20 microM) resulted in an enhancement of spontaneous [Ca2+]i and force transients. 3. In myometria of pregnant rats, although ryanodine had no effect in 40% of tissues studied it produced a small but significant enhancement of the integrated spontaneous [Ca2+]i and force transient in 60% of cases. The potentiating effects of CPA were enhanced in myometria of pregnant rats compared with non-pregnant rats, often resulting in maintained [Ca2+]i increases and contraction. 4. In zero external Ca2+, agonist-induced SR Ca2+ release resulted in transient increases in [Ca2+]i and force. The magnitude of these agonist-induced [Ca2+]i and force changes were significantly enhanced in myometria of pregnant rats. No evidence for agonist-induced Ca2+-independent force production was observed. 5. These results indicate that CICR plays little role in SR Ca2+ release from the myometrium, and that there are gestational-dependent alterations in the ability of SR Ca2+ mobilization to contribute to contractile activation. The implications of these findings for the co-ordination of myometrial [Ca2+]i signalling and contractility are discussed.
The Physiological Laboratory, University of Liverpool, Liverpool L69 3BX, UK.
M J
MJ
Taggart
S
S
Wray
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D009215:Myometrium / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D014590:Uterine Contraction / Q000502:physiology*; D014599:Uterus / Q000502:physiology*
D004791:Enzyme Inhibitors; D007211:Indoles; D012433:Ryanodine; D002110:Caffeine; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid