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 language | English |
---|---|
Pages (from-to) | 36-43 |
Number of pages | 8 |
Journal | Pflugers Archiv European Journal of Physiology |
Volume | 448 |
Issue number | 1 |
DOIs | |
Publication status | Published - Apr 2004 |
Externally published | Yes |
Keywords
- Chloride channels
- Contraction
- Niflumic acid
- Pacemaker
- Smooth muscle
ASJC Scopus subject areas
- Physiology
- Clinical Biochemistry
- Physiology (medical)