TY - JOUR T1 - Role of Calcium-Activated Potassium Channels in the Genesis of 3,4-Diaminopyridine-Induced Periodic Contractions in Isolated Canine Coronary Artery Smooth Muscles JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 974 LP - 983 DO - 10.1124/jpet.111.180687 VL - 338 IS - 3 AU - Yasumi Uchida AU - Yuko Maezawa AU - Yoshiro Maezawa AU - Yasuto Uchida AU - Fumitaka Nakamura Y1 - 2011/09/01 UR - http://jpet.aspetjournals.org/content/338/3/974.abstract N2 - We found that 3,4-diaminopyridine (3,4-DAP), a voltage-gated potassium channel (KV) 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 10−2 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 CaCl2 concentration in the chamber was ≤0.3 × 10−3 or ≥10−2 M. PCs were eliminated by a CaCl2 concentration ≥5 × 10−3 M or by lowering pH below 7.20 with HCl and recovered by the addition of iberiotoxin or charybdotoxin, which inhibit large-conductance calcium-activated potassium channels (KCa), 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 (CaV). Influx of Ca2+ through L-type CaV, which was opened because closing of KCa, secondary to 3,4-DAP-induced closing of KV, resulted in contraction; the intracellular Ca2+ increased by this influx opened KCa, leading to closure of CaV and consequent cessation of Ca2+ influx with resultant relaxation. These processes were repeated spontaneously to cause PCs. H+ and OH− were considered to act as the opener and closer of KCa, respectively. ER -