2-Aminoethoxydiphenyl borate inhibits KCl-induced vascular smooth muscle contraction

Eur J Pharmacol. 2006 Jul 17;541(3):177-83. doi: 10.1016/j.ejphar.2006.05.014.

Abstract

K(+)-depolarization (KCl)-activated Ca(2+) entry permitting sustained force-maintenance in tonic vascular smooth muscle has long been attributed solely to activation of L-type voltage-operated Ca(2+) channels (VOCs). We used the transient receptor potential channel (TRP) blocker, 2-aminoethoxydiphenyl borate (2-APB), to test the hypothesis that KCl activates additional Ca(2+) entry pathways. 2-APB alone caused a transient weak increase in force, a sustained weak increase in basal [Ca(2+)](i) and myosin light chain phosphorylation, and inhibition of KCl-induced force, [Ca(2+)](i) and myosin light chain phosphorylation. 2-APB did not appear to block VOCs, because 2-APB did not inhibit 30 nM Bay k 8644-induced increases in [Ca(2+)](i). Moreover, although 1 microM nifedipine abolished the increase in [Ca(2+)](i) produced by alpha-adrenergic receptor activation, 2-APB produced an additional reduction in [Ca(2+)](i) below the basal level. These data support the conclusion that membrane depolarization activates 2-APB-sensitive TRPs in addition to VOCs to permit strong force-maintenance in tonic vascular smooth muscle.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blotting, Western
  • Boron Compounds / pharmacology*
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Femoral Artery
  • Muscle Contraction / physiology*
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / physiology
  • Myosin Light Chains / metabolism
  • Nifedipine / pharmacology
  • Phosphorylation
  • Potassium Chloride / pharmacology*
  • Rabbits
  • Renal Artery
  • Transient Receptor Potential Channels / antagonists & inhibitors*

Substances

  • Boron Compounds
  • Calcium Channel Blockers
  • Myosin Light Chains
  • Transient Receptor Potential Channels
  • Potassium Chloride
  • 2-aminoethoxydiphenyl borate
  • Nifedipine
  • Calcium