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 (I_Cl-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 mu;M), and inhibited by the Cl^- channel blockers, niflumic acid (10 μM) and anthracene-9-carboxylic acid (9-AC, 100 μM). We therefore conclude that the pregnant rat myometrium contains Ca²⁺-activated Cl^- channels producing inward current in ∼30% 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.