Role of T-type Ca<SUP>2＋</SUP> Channels in the Spontaneous Phasic Contraction of Pregnant Rat Uterine Smooth Muscle

Role of T-type Ca<SUP>2＋</SUP> 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&#1356;M) 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 (&#1345;1G, &#1345;1H) 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.