BK(Ca) channel activation by membrane-associated cGMP kinase may contribute to uterine quiescence in pregnancy.
We investigated the influence of pregnancy on large-conductance calcium-activated potassium channel (BK(Ca)) activity (NP(o)) and on channel expression in membranes of isolated human myometrial smooth muscle cells. NP(o) in inside-out patches was higher in pregnant myometria (PM) compared with nonpregnant myometria (NPM), and the half-maximal activation potential was shifted by 39 mV to more negative potentials. This effect was not due to an enhanced BK(Ca) channel expression. In the presence of cAMP kinase (PKA) or cGMP kinase (PKG), NP(o) increased in patches from PM but decreased in those from NPM. Western blot analysis and use of a specific PKG inhibitor (1 microM KT-5823) verified the existence of a partially active membrane-associated PKG. Inhibition of PKA by 100 nM PKI, the inhibitory peptide of PKA, had no effect on NP(o). 8-p-Chlorophenylthio-cGMP (8-pCPT-cGMP) hyperpolarized cells from PM. This effect was abolished by iberiotoxin, a specific blocker of BK(Ca) channels. It is concluded that an endogenous, membrane-bound PKG in myometrial cells specifically enhances BK(Ca) channel activity during pregnancy and thus may contribute to uterine quiescence during pregnancy.
Zhou
X B
XB
Abteilung Pharmakologie für Pharmazeuten, Universitäts-Krankenhaus Eppendorf, D-20246 Hamburg, Germany.
Wang
G X
GX
Ruth
P
P
Hüneke
B
B
Korth
M
M
D000470:Alkaloids / Q000494:pharmacology; D002227:Carbazoles; D002462:Cell Membrane / Q000737:chemistry / Q000201:enzymology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009215:Myometrium / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D007752:Obstetric Labor, Premature / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated; D011247:Pregnancy; D013873:Thionucleotides / Q000494:pharmacology; D014590:Uterine Contraction / Q000502:physiology*
D000470:Alkaloids; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D013873:Thionucleotides; C073601:KT 5823; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; C064719:iberiotoxin; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP