title: 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(-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 CaCl(2) concentration in the chamber was ≤ 0.3 × 10(-3) or ≥ 10(-2) M. PCs were eliminated by a CaCl(2) 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 (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(2+) through L-type Ca(V), which was opened because closing of K(Ca), secondary to 3,4-DAP-induced closing of K(V), resulted in contraction; the intracellular Ca(2+) increased by this influx opened K(Ca), leading to closure of Ca(V) and consequent cessation of Ca(2+) 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 K(Ca), respectively.
authors.affiliation: Japan Foundation for Cardiovascular Research, Funabashi, Japan. uchiy@ta2.so-net.ne.jp
authors.forename: Yasumi
authors.initials: Y
authors.lastname: Uchida
authors.forename: Yuko
authors.initials: Y
authors.lastname: Maezawa
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Maezawa
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Uchida
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Nakamura
mesh_terms: D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000077770:Amifampridine; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008931:Mitochondria, Muscle / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
chemical_list: D000318:Adrenergic beta-Agonists; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D007473:Ion Channels; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D019831:Sodium-Calcium Exchanger; D015761:4-Aminopyridine; D000254:Sodium-Potassium-Exchanging ATPase; D002122:Calcium Chloride; D000077770:Amifampridine