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In the myometrium SR Ca(2+) depletion promotes an increase in force but unlike several other smooth muscles, there is no Ca(2+) sparks-STOCs coupling mechanism to explain this. Given the importance of the control of contractility for successful parturition, we have examined, in pregnant rat myometrium, the effects of SR Ca(2+)-ATPase (SERCA) inhibition on the temporal relationship between action potentials, Ca(2+) transients and force. Simultaneous recording of electrical activity, calcium and force showed that SERCA inhibition, by cyclopiazonic acid (CPA 20 μM), caused time-dependent changes in excitability, most noticeably depolarization and elevations of baseline [Ca(2+)]i and force. At the onset of these changes there was a prolongation of the bursts of action potentials and a corresponding series of Ca(2+) spikes, which increased the amplitude and duration of contractions. As the rise of baseline Ca(2+) and depolarization continued a point was reached when electrical and Ca(2+) spikes and phasic contractions ceased, and a maintained, tonic force and Ca(2+) was produced. Lanthanum, a non-selective blocker of store-operated Ca(2+) entry, but not the L-type Ca(2+) channel blocker nifedipine (1-10 μM), could abolish the maintained force and calcium. Application of the agonist, carbachol, produced similar effects to CPA, i.e. depolarization, elevation of force and calcium. A brief, high concentration of carbachol, to cause SR Ca(2+) depletion without eliciting receptor-operated channel opening, also produced these results. The data obtained suggest that in pregnant rats SR Ca(2+) release is coupled to marked Ca(2+) entry, via store operated Ca(2+) channels, leading to depolarization and enhanced electrical and mechanical activity.

Original publication

DOI

10.1016/j.ceca.2014.07.003

Type

Journal article

Journal

Cell Calcium

Publication Date

09/2014

Volume

56

Pages

188 - 194

Keywords

Smooth muscle, Uterus, Sarcoplasmic reticulum, Action Potentials, Animals, Caffeine, Calcium, Calcium Channel Blockers, Calcium Channels, Calcium Signaling, Carbachol, Cells, Cultured, Cholinergic Agonists, Electric Stimulation, Enzyme Inhibitors, Female, Indoles, Membrane Potentials, Myometrium, Nifedipine, Phosphodiesterase Inhibitors, Pregnancy, Rats, Rats, Wistar, Sarcoplasmic Reticulum, Sarcoplasmic Reticulum Calcium-Transporting ATPases