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

K. Jones, A. Shmygol, S. Kupittayanant, Susan Wray

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

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 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.

Original languageEnglish
Pages (from-to)36-43
Number of pages8
JournalPflugers Archiv European Journal of Physiology
Volume448
Issue number1
DOIs
Publication statusPublished - Apr 2004
Externally publishedYes

Keywords

  • Chloride channels
  • Contraction
  • Niflumic acid
  • Pacemaker
  • Smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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