Calcium-activated K+ channels as modulators of human myometrial contractile activity.
The role of Ca(2+)-activated potassium (KCa) channels in the regulation of membrane potential, intracellular free calcium ([Ca2+]i) and contraction was investigated in uterine smooth muscle and myometrial cells. In an immortalized human myometrial cell line, oxytocin increased [Ca2+]i and [3H]inositol phosphate formation. Relaxin attenuated the oxytocin-induced increase in [Ca2+]i. In cell-attached patches, membrane depolarization activated a large-conductance KCa channel (179 +/- 4 pS). Iberiotoxin (IbTX), a potent blocker of "maxi" KCa channels (A. Galvez, G. Gimenez-Gallego, J. P. Reuben, L. Roy-Contanciin, P. Feigenbaum, G. J. Kaczorowski, and M. L. Garcia. J. Biol. Chem. 265: 11083-11090, 1990) produced long closed events (approximately 6 min) in these channels. In agreement with this blockage, IbTX depolarized the cells by 9.8 +/- 2.8 mV and caused a dose-dependent increase in [Ca2+]i with a half-maximal effective concentration of 0.79 nM. IbTX also caused phasic contractions in human myometrial strips and increased both the frequency and force of spontaneous contractions in estrogen-primed rat myometrial strips. Moreover, myometrial contractility was also affected by 1 mM tetraethylammonium, a concentration that blocks uterine smooth muscle KCa channels when applied to the extracellular side (G. J. Perez, L. Toro, S. D. Erulkar, and E. Stefani. Am. J. Obstet. Gynecol. 168: 652-660, 1993). These results strongly suggest that the large conductance KCa channels may actively participate in the control of human myometrial cell membrane potential and [Ca2+].
Anwer
K
K
Department of Biochemistry, University of Texas Medical School at Houston.
Oberti
C
C
Perez
G J
GJ
Perez-Reyes
N
N
McDougall
J K
JK
Monga
M
M
Sanborn
B M
BM
Stefani
E
E
Toro
L
L
D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D004594:Electrophysiology; D005260:Female; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009215:Myometrium / Q000166:cytology / Q000378:metabolism; D009994:Osmolar Concentration; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D014590:Uterine Contraction / Q000187:drug effects / Q000502:physiology*
D007295:Inositol Phosphates; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C064719:iberiotoxin; D002118:Calcium