Carboxyeosin decreases the rate of decay of the [Ca2+]i transient in uterine smooth muscle cells isolated from pregnant rats.
In myometrial smooth muscle cells the rate of decline of intracellular calcium ([Ca2+]i) is determined by Ca2+ extrusion from the cell and uptake into intracellular stores. The relative quantitative contribution of these processes however, has not been established. We therefore examined the effect of the sarcolemmal Ca2+ pump inhibitor, carboxyeosin, on the rate of the [Ca2+]i transient decline in myocytes isolated from pregnant rat uterus. Indo-1 was used in conjunction with the whole-cell patch-clamp technique to measure [Ca2+]i simultaneously with transmembrane calcium current (ICa). [Ca2+]i transients were elicited by repetitive membrane depolarization to simulate the natural pattern of uterine electrical activity. The rate of [Ca2+]i removal was calculated from the falling phase of the [Ca2+]i transient. Pre-treatment of the cells with 2 microM carboxyeosin led to a marked decrease in the rate of [Ca2+]i transient decay, suggesting that the sarcolemmal Ca2+ pump is involved in the calcium extrusion process. Removal of the extracellular Na also decreased the rate of [Ca2+]i decay, indicating an important role for the Na+/Ca2+ exchange. When both the sarcolemmal Ca2+ pump and Na+/Ca2+ exchange were inhibited the cell failed to restore [Ca2+]i after the stimulation. Comparison of the rate constants of [Ca2+]i decay in control conditions and after carboxyeosin treatment shows that approximately 30% of [Ca2+]i decay is due to the sarcolemmal calcium pump activity. The remaining 70% can be attributed to the activity of Na+/Ca2+ exchanger and the intracellular calcium stores.
Shmigol
A
A
Department of Physiology, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK.
Eisner
D A
DA
Wray
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004801:Eosine Yellowish-(YS) / Q000494:pharmacology*; D005260:Female; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000201:enzymology; D012964:Sodium / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D004791:Enzyme Inhibitors; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D000252:Calcium-Transporting ATPases; D002118:Calcium; D004801:Eosine Yellowish-(YS)