Calcium-activated chloride currents prolongs the duration of contractions in pregnant rat myometrial tissue.
We investigated the importance of pharmacologically blocking calcium-activated chloride (I(Cl(Ca))) and L-type calcium currents on isometric contractions of strips of D21 pregnant rat myometrial tissue, while simultaneously measuring the electrical activity of the tissue strips with extracellular contact electrodes. When measured with contact electrodes, the duration of the spiking activity directly reflects the duration of the tissue-level plateau potential. We correlated the number of spikes, durations of spiking activity, and the spiking frequencies with changes of the area under the force curves as a function of exposure to low doses of anthracene-9-carboxylate (9-AC, a non-specific Cl channel blocker), chlorotoxin (a specific I(Cl(Ca)) blocker) and nifedipine (an L-type calcium channel blocker). The area under the force curve was measured only during spiking electrical activity, thereby separating pharmacological effects on tissue relaxation from those that modulate force production. Blocking chloride channels reduced impulse, shortened the duration of spiking activity, and reduced the number of spikes generated in each contraction. This was observed without a change in the frequency of spike production or a reduction of peak force. Nifedipine reduced impulse, shortened the duration of spiking activity, and reduced the number of spikes. In contrast to chloride channel blockade, nifedipine reduced maximum spike frequency and peak force. Taken together, our data suggest that blocking L-type calcium channels reduces impulse directly by reducing peak force, and indirectly by reducing activation of I(Cl(Ca)) , which shortens the duration of the contraction.
Young
Roger C
RC
Department of Obstetrics and Gynecology, University of Vermont, Burlington, Vermont 05405, USA. roger.young@uvm.edu
Bemis
Adam
A
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D005260:Female; D008564:Membrane Potentials; D053580:Muscle Strength; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D012604:Scorpion Venoms / Q000494:pharmacology; D013997:Time Factors; D014590:Uterine Contraction / Q000187:drug effects
D000873:Anthracenes; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018118:Chloride Channels; D002712:Chlorides; D012604:Scorpion Venoms; C091539:Chlorotoxin; C010030:9-anthroic acid; D009543:Nifedipine