Role of Calcium-Activated Potassium Channels in the Genesis of 3,4-Diaminopyridine-Induced Periodic Contractions in Isolated Canine Coronary Artery Smooth Muscles

Abstract

We found that 3,4-diaminopyridine (3,4-DAP), a voltage-gated potassium channel (K V ) inhibitor, elicits pH-sensitive periodic contractions (PCs) of coronary smooth muscles. Underlying mechanisms of PCs, however, remained to be elucidated. The present study was performed to examine the roles of ion channels in the genesis of PCs. To determine the electromechanical changes of smooth muscles, isolated coronary arterial rings from beagles were suspended in organ chambers filled with Krebs-Henseleit solution, and 10 Ϫ2 M 3,4-DAP was added to elicit PCs. 3,4-DAP caused periodic spike-and-plateau depolarization accompanied by contraction. PCs were not produced when the CaCl 2 concentration in the chamber was Յ0.3 ϫ 10 Ϫ3 or Ն10 Ϫ2 M. PCs were eliminated by a CaCl 2 concentration Ն5 ϫ 10 Ϫ3 M or by lowering pH below 7.20 with HCl and recovered by the addition of iberiotoxin or charybdotoxin, which inhibit large-conductance calciumactivated potassium channels (K Ca ), or by elevating pH above 7.35 with NaOH. PCs, as well as the spike-and-plateau depolarization, were eliminated by nifedipine, which inhibits L-type voltage-gated calcium channels (Ca V ). Influx of Ca 2ϩ through L-type Ca V , which was opened because closing of K Ca , secondary to 3,4-DAPinduced closing of K V , resulted in contraction; the intracellular Ca 2ϩ increased by this influx opened K Ca , leading to closure of Ca V and consequent cessation of Ca 2ϩ influx with resultant relaxation. These processes were repeated spontaneously to cause PCs. H ϩ and OH Ϫ were considered to act as the opener and closer of K Ca , respectively.

The Spasmolytic Effect of Astragalus Sarcocolla on the Intestinal Smooth Muscles of Rabbit In Vitro: Potassium Channel Opening

“…In this study, ASE was tested for its antispasmodic effect, and it was found that it has serious antispasmodic potential. Most of the plants that are used as antispasmodics work mainly by two mechanisms: 1) by blocking the calcium channels in the intestines and causing relaxation and 2) by the opening of potassium channels and producing relaxant effect in the intestine [21].…”