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

Abstract

Although extracellular Ca2+ entry through the voltage-dependent Ca2+ channels plays an important role in the spontaneous phasic contractions of the pregnant rat myometrium, the role of the T-type Ca2+ channels has yet to be fully identified. The aim of this study was to investigate the role of the T-type Ca2+ channel in the spontaneous phasic contractions of the rat myometrium. Spontaneous phasic contractions and [Ca2+]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 Ca2+ channel mRNAs or protein levels was measured. Cumulative addition of low concentrations (<1 micrometer) of nifedipine, a L-type Ca2+ channel blocker, produced a decrease in the amplitude of the spontaneous Ca2+ transients and contractions with no significant change in frequency. The mRNAs and proteins encoding two subunits (alpha1G, alpha1H) of the T-type Ca2+ 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 Ca2+ transients and contractions. Mibefradil, NNC 55-0396 or nickel also attenuated the slope of rising phase of spontaneous Ca2+ transients consistent with the reduction of the frequency. It is concluded that T-type Ca2+ channels are expressed in the pregnant rat myometrium and may play a key role for the regulation of the frequency of spontaneous phasic contractions.