Role of T-type Ca2+ Channels in the Spontaneous Phasic Contraction of Pregnant Rat Uterine Smooth Muscle

Although extracellular Ca(2+) entry through the voltage-dependent Ca(2+) channels plays an important role in the spontaneous phasic contractions of the pregnant rat myometrium, the role of the T-type Ca(2+) channels has yet to be fully identified. The aim of this study was to investigate the role of the T-type Ca(2+) channel in the spontaneous phasic contractions of the rat myometrium. Spontaneous phasic contractions and [Ca(2+)](i) were measured simultaneously in the longitudinal strips of female Sprague-Dawley rats late in their pregnancy (on day 18~20 of gestation: term=22 days). The expression of T-type Ca(2+) channel mRNAs or protein levels was measured. Cumulative addition of low concentrations (<1 microM) of nifedipine, a L-type Ca(2+) channel blocker, produced a decrease in the amplitude of the spontaneous Ca(2+) transients and contractions with no significant change in frequency. The mRNAs and proteins encoding two subunits (alpha1G, alpha1H) of the T-type Ca(2+) channels were expressed in longitudinal muscle layer of rat myometrium. Cumulative addition of mibefradil, NNC 55-0396 or nickel induced a concentration-dependent inhibition of the amplitude and frequency of the spontaneous Ca(2+) transients and contractions. Mibefradil, NNC 55-0396 or nickel also attenuated the slope of rising phase of spontaneous Ca(2+) transients consistent with the reduction of the frequency. It is concluded that T-type Ca(2+) channels are expressed in the pregnant rat myometrium and may play a key role for the regulation of the frequency of spontaneous phasic contractions.