Regulation of potassium channels in coronary arterial smooth muscle by endothelium-derived vasodilators.
Recent studies have suggested that coronary endothelial cells produce and release nitric oxide (NO), prostaglandin I2, and epoxyeicosatrienoic acids (EETs). These endothelium-derived vasodilators play an important role in the control of coronary vascular tone. However, the mechanism by which these endothelium-derived vasodilators cause relaxation of coronary arterial smooth muscle has yet to be determined. This study characterized and compared the effects of NO, prostaglandin I2, and 11,12-EET on the two main types of potassium channels in small bovine coronary arterial smooth muscle: the large conductance Ca(2+)-activated K+ channels (KCa) and 4-aminopyridine-sensitive delayed rectifier K+ channels (Kdrf). In cell-attached patches, nonoate, an NO donor, activated both KCa and Kdrf channels. The open probability of both KCa and Kdrf channels increased 10- to 25-fold when nonoate was added to the bath at concentrations of 10(-6) to 10(-4) mol/L. 11,12-EET (10(-8) to 10(-4) mol/L) also increased the activity of the KCa channels in a concentration-dependent manner, but it had no effect on the activity of the Kdrf channels, even in the highest concentration studied (10(-4) mol/L). In contrast to the effect of 11,12-EET, iloprost, a prostaglandin I2 analogue (10(-6) to 10(-4) mol/L), produced a concentration-dependent increase in the activity of Kdrf channels without affecting the KCa channels. In conclusion, all three endothelium-derived vasodilators act to open potassium channels; however, the channel types that they affect are different. NO activates both KCa and Kdrf channels; 11,12-EET activates only the KCa channels; and prostaglandin I2 activates only the Kdrf channels.
Li
P L
PL
Department of Pharmacology, Medical College of Wisconsin, Milwaukee, 53226, USA. pli@post.its.mcw.edu
Zou
A P
AP
Campbell
W B
WB
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology*
D010455:Peptides; D015221:Potassium Channels; D009569:Nitric Oxide; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; C064719:iberiotoxin; D011464:Epoprostenol; D015126:8,11,14-Eicosatrienoic Acid