Agonist mobilization of sarcoplasmic reticular calcium in smooth muscle: functional coupling to the plasmalemmal Na+/Ca2+ exchanger?

There is a close association of peripheral sarcoplasmic reticulum (SR), containing IP3 receptors, and regions of the plasma membrane enriched in the Na+/Ca2+ exchanger in smooth muscle. We have tested the possibility in rat uterine smooth muscle that Ca2+ released from the SR is preferentially removed from the cytosol by the Na+/Ca2+ exchanger. In Ca(2+)-free solution, carbachol stimulation of myometria of non-pregnant rats resulted in transient increases in [Ca2+]i and force due entirely to the release of SR Ca2+. Inhibition of Na+/Ca2+ exchange by removal of extracellular Na+ did not alter the agonist-induced transients suggesting that Na+/Ca2+ exchange was not involved in the removal of SR released Ca2+. However, in myometria of pregnant rats, Na+/Ca2+ exchange inhibition resulted in changes in the agonist-induced [Ca2+]i transient profiles. The peak amplitude, duration and integral of carbachol-induced [Ca+]i transients were enhanced in Ca(2+)-free/Na(+)-free solution without significantly affecting force transients. The lower rate of decay of [Ca2+]i transients in Na(+)-free solution leads us to suggest that up to 35% of the SR released Ca2+ may be extruded by the Na+/Ca2+ exchanger in myometria of pregnant rats. Thus, in uterine smooth muscle, there is a gestational-dependent coupling of SR releasable Ca2+ and plasmalemmal Na+/Ca2+ exchange activity.