Characterization of an oxytocin-induced rise in [Ca2+]i in single human myometrium smooth muscle cells.
The effect of the uterotonic pituitary hormone oxytocin on the regulation of intracellular calcium concentration ([Ca2+]i) was studied in single cells of a smooth muscle cell line derived from human non-pregnant myometrium. [Ca2+]i was measured with fluorescence microscopy, and by recording the activity of Ca(2+)-activated potassium currents (IK(Ca)) on the whole cell and single channel level. Oxytocin induced a rapid and transient increase in [Ca2+]i that was paralleled by a significant increase in IK(Ca) activity. After removal of extracellular Ca2+, repetitive stimulation with oxytocin did not alter the [Ca2+]i transients initially; however, their amplitude became progressively smaller and the response was eventually abolished completely, indicating that oxytocin increased [Ca2+]i by release of Ca2+ from intracellular stores. Nifedipine did not alter the oxytocin-induced [Ca2+]i-transients suggesting that oxytocin failed to activate Ca2+ entry through voltage-operated Ca2+ channels. Thapsigargin abolished the oxytocin-induced [Ca2+]i transient. Caffeine alone had no effect on [Ca2+]i, however it diminished the oxytocin-induced [Ca2+]i transients. Ryanodine did not affect the oxytocin response indicating that these cells lack release of Ca2+ from the ryanodine receptor release channel. These results demonstrate that oxytocin elicited [Ca2+]i transients predominantly through Ca2+ release from thapsigargin-sensitive stores, presumably by activating an inositol 1,4,5-trisphosphate dependent pathway.
Holda
J R
JR
Department of Physiology, Loyola University Chicago, Maywood, Illinois 60153, USA.
Oberti
C
C
Perez-Reyes
E
E
Blatter
L A
LA
D001692:Biological Transport / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D009130:Muscle, Smooth / Q000166:cytology*; D009215:Myometrium / Q000166:cytology*; D009543:Nifedipine / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology*; D012433:Ryanodine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D012433:Ryanodine; D002110:Caffeine; D010121:Oxytocin; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D009543:Nifedipine; D002118:Calcium