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

Abstract

We investigated the role of the T‐type Ca2+ channel in spontaneous phasic contraction (SPC) of the rat myometrium. SPC and [Ca2+]i were measured simultaneously in longitudinal strips of female rats in late pregnancy. Expression of T‐type Ca2+ channel subunits was examined by using RT‐PCR technique. The SPC and [Ca2+]i were completely inhibited by removal of external Ca2+and treatment of nifedipine. T‐type Ca2+ channel blocker, 1μM mibefradil and 5μM NNC 55‐0396 evoked concentration‐dependent inhibition of SPC and [Ca2+]i and these blockers decreased the amplitude and frequency of SPC as well as [Ca2+]i. On the other hand, 100μM nickel, a blocker of T‐type Ca2+ channel, decreased the frequency but not the amplitude of SPC. Pretreatment of mibefradil and NNC 55‐0396 significantly attenuated the KCl‐induced increase in contraction and [Ca2+]i, respectively, but nickel had no effect on KCl‐induced increase in contraction and [Ca2+]i. All of three T‐type Ca2+ channel blockers decreased the slope of rising phase of SPC and [Ca2+]i. In RT‐PCR analysis, T‐type Ca2+ channel subunits, Cav3.1 and Cav3.2, were expressed in pregnant rat myometrium. The present study demonstrates that T‐type Ca2+ channel involves in the generation of SPC of pregnant rat myometrium. Furthermore, Ca2+influx through T‐type Ca2+ channel may play a key role for the slow depolarization.

A molecular signature of tissues with pacemaker activity in the heart and upper urinary tract involves coexpressed hyperpolarization‐activated cation and T‐type Ca 2+ channels

“…Low‐voltage‐gated TTC channels drive a depolarizing conductance that is activated by small HCN‐dependent pacemaker depolarizations, and studies using organic inhibitors of TTC channels show that inhibition of TTC channel activity decreases the heart rate (45, 46). Therefore, we tested whether the frequency of UUT contractions is decreased by either of the two specific organic inhibitors of TTC channels, R(–)efonidipine (47, 48) and NNC 55–0396 (49, 50) (Fig. 6 E ).…”

Characterization of the tissue‐level Ca2+ signals in spontaneously contracting human myometrium

“…In many types of smooth muscle, T-type Ca 2+ channels are involved in a vast variety of cellular functions such as pacemaking, proliferation, contraction, etc. [28,[34][35][36][37]. An increase in the T-type Ca 2+ channel expression has been described in proliferating pulmonary artery myocytes [35].…”

TRPC1, STIM1, and ORAI Influence Signal-Regulated Intracellular and Endoplasmic Reticulum Calcium Dynamics in Human Myometrial Cells1

“…T-type Ca 2þ channels have been implicated in the initiation of action potentials and in spontaneous contractile activity in myometrium [26,40]. With time in culture, myometrial cells such as those used in this study tend to lose robust responses to iso-osmotic KCldependent depolarization, indicative of dampened voltagedependent responses.…”

“…L-type Ca 2þ channel blockers inhibit Ca 2þ entry following myometrial cell membrane depolarization and have marked inhibitory effects on spontaneous and agonist-induced uterine contractile activity [1,26,[38][39][40]. T-type Ca 2þ channels have been implicated in the initiation of action potentials and in spontaneous contractile activity in myometrium [26,40].…”