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 Ca(2+)-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 Ca(2+) (but not Ba(2+)) entry through L-type Ca(2+) channels, enhanced by the Ca(2+) channel agonist Bay K8644 (2 microM), and inhibited by the Cl(-) channel blockers, niflumic acid (10 microM) and anthracene-9-carboxylic acid (9-AC, 100 microM). We therefore conclude that the pregnant rat myometrium contains Ca(2+)-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 Ca(2+) transients. Neither 9-AC nor niflumic acid had any effect on high-K-invoked contractions. Taken together these data suggest that Ca(2+)-activated Cl(-) channels are activated by Ca(2+) entry and play a functionally important role in myometrium, probably by contributing to membrane potential and firing frequency (pacemakers) in these cells.
Jones
K
K
Department of Physiology, The University of Liverpool, Liverpool, L69 3BX, UK.
Shmygol
A
A
Kupittayanant
S
S
Wray
Susan
S
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D065101:Chloride Channel Agonists; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D008564:Membrane Potentials / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D009215:Myometrium / Q000166:cytology*; D011247:Pregnancy; D051381:Rats; D014590:Uterine Contraction / Q000502:physiology
D000873:Anthracenes; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D065101:Chloride Channel Agonists; D018118:Chloride Channels; D001464:Barium; C010030:9-anthroic acid; D002118:Calcium