Background: 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 mechanism(s) of PCs however remained to be elucidated. Purpose: The present study was performed to examine the roles of ion channels in the genesis of PCs. Methods: 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 mol/L 3,4-DAP was added to elicit PCs. Results: 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 ≥ 10-2mol/L. PCs were eliminated by a CaCl2 concentration ≥ 5×10-3 mol/L 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). Conclusions: Influx of Ca(2+) through L-type CaV, which was opened because of closing of KCa secondary to 3,4-DAP-induced closing of KV, resulted in contraction; the intracellular Ca(2+) increased by this influx opened KCa, leading to closure of CaV and consequent cessation of Ca(2+) influx, with resultant relaxation; and these processes were repeated spontaneously to cause PCs. H(+) and OH(-) were considered to act opener and closer of KCa, respectively.
- Calcium ions
- calcium-activated potassium channels
- coronary smooth muscles
- periodic contractions
- voltage-gated calcium channels
- Received February 17, 2011.
- Revision received June 13, 2011.
- Accepted June 14, 2011.
- The American Society for Pharmacology and Experimental Therapeutics