In smooth muscle cells, the SR is an important regulator of cytosolic Ca²⁺, membrane excitability, and a source of Ca²⁺ for contraction. In some smooth muscles, important developmental differences have been found in the size and function of the SR (Hillemeier et al. 1991; Nakanishi et al. 1997). There are, however, no comparative data on the myometrium. The aim of this study is therefore to investigate the role of neonatal uterine SR, to further our understanding of the control of uterine activity.

Simultaneous measurements of intracellular Ca²⁺ ([Ca²⁺]_i) and force were made on strips of uterus taken from 2-day and 10-day-old neonatal and non-pregnant adult rats, after humane killing. The presence of an SR Ca²⁺ store in the neonate was determined by using (i) 20 mM cyclopiazonic acid (CPA), a specific inhibitor of the SR Ca²⁺ pump, and (ii) 100 mM carbachol, in the presence and absence of extracellular Ca²⁺. Data were normalised to high-K⁺ (150 mM)-induced contractions, and are expressed as means ± S.E.M.; significance was tested using Student’s unpaired t test, with significance taken at P < 0.05; n is number of animals.

The neonatal uterus was spontaneously active, producing Ca²⁺ transients followed by phasic contractions at a frequency of 4.5 ± 0.7 per 10 min (37 °C). Emptying the SR with CPA significantly increased this frequency and basal [Ca²⁺]_i and force to 174 ± 4 and 241 ± 12 % (n = 4), respectively. Carbachol induced significantly greater maximal [Ca²⁺]_i and force in neonate compared with adult myometrium (140 ± 4 vs. 113 ± 10 % [Ca²⁺]_i and 182 ± 19 vs. 120 ± 7 % force; n = 6, respectively). There was also marked force production after [Ca²⁺]_i had returned to basal levels in the neonates (9.7 ± 1.8 vs. 1.4 ± 0.5 min in the adult). Oxytocin (100 nM) produced little or no effect on the neonatal uterus but greatly potentiated force and [Ca²⁺]_i in the adults. In zero Ca²⁺ solutions, carbachol-induced SR Ca²⁺ release increased myometrial [Ca²⁺]_i by 122 ± 5 % in 2-day neonates, 77 ± 3 % in 10-day neonates and 44 ± 5 % in adult rats compared with high-K⁺ controls (n = 5).

These data clearly show that spontaneous force and Ca²⁺ transients and a functional SR Ca²⁺ store exist in neonatal rat uterus. As with adult uterus, this SR Ca²⁺ seems to limit spontaneous contraction, suggesting a negative feedback mechanism. Significantly more SR Ca²⁺ is released in neonatal rat myometrium than adult myometrium and the younger the rat, the more this release is. The neonatal uterus has a greater response to carbachol than adult uterus possibly due to (i) the relatively large size of the functional SR store in the neonate and/or (ii) increased carbachol-induced sensitisation of the contractile apparatus in the neonate.

Thanks to the MRC for their support.

All procedures accord with current UK legislation.