Forskolin inhibition of K+ current in pregnant rat uterine smooth muscle cells.
Two kinds of outward K+ currents were examined in single smooth muscle cells from pregnant rat uterus, using whole-cell voltage clamp. The first and faster component was more sensitive to 4-aminopyridine (4-AP), whereas the second and slower (delayed) component was more sensitive to tetraethylammonium (TEA). A possible third K+ component (Ca activated K+ current) was not recorded as the pipette solution included EGTA. Forskolin inhibited the outward current in a concentration-dependent manner (50% inhibition occurred at about 30 microM); it affected the delayed component rather than the fast component. 8-Bromo-cAMP did not alter the outward current. In addition, inhibitors of protein kinase A and GDP-beta S and GTP-gamma S did not affect the forskolin-induced inhibition. These results indicate that forskolin inhibition of the delayed component of the outward current is independent of cAMP generation in the pregnant rat myometrial cells. Therefore, forskolin seems to directly inhibit specific K+ channels, as was reported for several other cell types.
Inoue
Y
Y
Department of Physiology and Biophysics, University of Cincinnati, OH 45267.
Shimamura
K
K
Sperelakis
N
N
D015761:4-Aminopyridine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000031:analogs & derivatives / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects*
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D013873:Thionucleotides; C034883:guanosine 5'-O-(2-thiotriphosphate); D006153:Guanosine Diphosphate; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019789:Tetraethylammonium; C023427:guanosine 5'-O-(2-thiodiphosphate); D015761:4-Aminopyridine