Cromakalim activates the K(ATP) and enhances spontaneous transient outward potassium currents in rat saphenous arterial myocytes.
Potassium channel openers, e.g. cromakalim are held to relax smooth muscle by hyperpolarizing the cell membrane via activation of ATP-sensitive K(+) (K(ATP)) channels. A recent report indicates that members of this group dilate cerebral arteries also by enhancing the K(Ca)-based spontaneous transient outward currents (STOCs) through the activation of mitochondrial K(ATP) channels. We extended the study to rat saphenous arterial myocytes, a model for peripheral resistance vessels, to investigate the effects of cromakalim on K(ATP) and STOCs, and the underlaying mechanisms. Smooth muscle myocytes were enzymatically dissociated from the saphenous branch of the femoral artery. Macroscopic currents were recorded from acutely isolated cells using the perforated-patch and whole-cell variants of the patch-clamp technique. Predictably metabolic inhibitors and cromakalim activated a background K(+) current blocked by glibenclamide, identified as the K(ATP) channel. However, in addition, cromakalim markedly increased the amplitude and frequency of STOCs. The latter action was not sensitive to the specific K(ATP) channel blocker glibenclamide, excluding the participation of mitocondrial K(ATP) channels in this action. In conclusion, this study suggests that, in addition to the opening of K(ATP) channels, the increased STOC activity may have an important role in the vasorelaxing action of cromakalim, but through a mechanism different from that reported on cerebral artery.
Fioretti
Bernard
B
Dipartimento di Biologia Cellulare e Ambientale, Universita' di Perugia, via Pascoli 1, I-06123 Perugia, Italy.
Trequattrini
Carlo
C
Sforna
Luigi
L
Harper
Alexander
A
Catacuzzeno
Luigi
L
Franciolini
Fabio
F
D000818:Animals; D001158:Arteries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019806:Cromakalim / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
D015221:Potassium Channels; D014665:Vasodilator Agents; C117780:mitochondrial K(ATP) channel; D019806:Cromakalim; D011188:Potassium; D005905:Glyburide