Electrophysiological characterization and functional importance of calcium-activated chloride channel in rat uterine myocytes

In order to better understand the mechanisms underlying excitation of the uterus, we have elucidated the characteristics and functional importance of Ca2+-activated Cl- currents (ICl-Ca) in pregnant rat myometrium. In 101/320 freshly isolated myocytes, there was a slowly inactivating tail current (162+/-48 pA) upon repolarization following depolarising steps. This current has a reversal potential close to that for chloride, and was shifted when [Cl-] was altered. It was activated by Ca2+ (but not Ba2+) entry through L-type Ca2+ channels, enhanced by the Ca2+ channel agonist Bay K8644 (2 muM), and inhibited by the Cl- channel blockers, niflumic acid (10 muM) and anthracene-9-carboxylic acid (9-AC, 100 muM). We therefore conclude that the pregnant rat myometrium contains Ca2+-activated Cl- channels producing inward current in similar to30% of its cells. When these channels were inhibited by niflumic acid or 9-AC in intact tissues, the frequency of spontaneous contractions, was significantly reduced. Niflumic acid was also shown to inhibit oxytocin-induced contractions and Ca2+ transients. Neither 9-AC nor niflumic acid had any effect on high-K-invoked contractions. Taken together these data suggest that Ca2+-activated Cl- channels are activated by Ca2+ entry and play a functionally important role in myometrium, probably by contributing to membrane potential and firing frequency (pacemakers) in these cells.