Mechanism of barium-induced contraction in the vascular smooth muscle of rabbit aorta

Br J Pharmacol. 1986 Aug;88(4):821-6. doi: 10.1111/j.1476-5381.1986.tb16255.x.

Abstract

In a solution containing 1.5 mM Ca2+, cumulative application of 0.3-10.0 mM Ba2+ induced a concentration-dependent contraction of the rabbit aorta. This contraction was reduced by the Ca2+ channel inhibitors, verapamil (10(-6) M), nifedipine (10(-7) M) and lanthanum (2.0 mM), and was potentiated by the Ca2+ channel facilitator, Bay K8644 (10(-7) M). In a Ca2+-free solution containing EGTA (1.0 mM), cumulative application of Ba2+ still induced a concentration-dependent contraction, the maximum contractile tension of which was comparable to that in the presence of 1.5 mM Ca2+. The Ba2+-induced contraction which was not dependent on the external Ca2+ was also inhibited by verapamil, nifedipine and lanthanum and was potentiated by Bay K8644. A high concentration (65.4 mM) of K+ potentiated this Ba2+-induced contraction whereas noradrenaline (10(-6) M) did not have such an effect. In order to deplete the releasable Ca2+ store in the cell, the muscle strip was treated with noradrenaline (10(-6) M) and/or caffeine (20.0 mM) in a Ca2+-free solution. In such a Ca2+-depleted muscle, Ba2+ still induced a contraction of a similar magnitude to that without such treatment. Further, the second application of Ba2+ in a Ca2+-free solution induced a similar contraction to that induced by the first application of Ba2+. These results suggest that Ba2+ depolarizes the cell membrane and opens the voltage-dependent Ca2+ channels resulting in a Ca2+ influx in the presence of Ca2+. In the absence of external Ca2+, Ba2+ may enter the cell through the voltage-dependent Ca2+ channels and induce contraction without mobilizing the Ca2+ store which is sensitive to noradrenaline and caffeine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Animals
  • Barium / pharmacology*
  • Calcium / metabolism
  • Dose-Response Relationship, Drug
  • Ion Channels / drug effects
  • Ion Channels / metabolism
  • Lanthanum / pharmacology
  • Male
  • Muscle Contraction / drug effects*
  • Muscle, Smooth, Vascular / drug effects*
  • Nifedipine / analogs & derivatives
  • Nifedipine / pharmacology
  • Norepinephrine / pharmacology
  • Potassium / pharmacology
  • Rabbits
  • Verapamil / pharmacology

Substances

  • Ion Channels
  • Barium
  • Lanthanum
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Verapamil
  • Nifedipine
  • Potassium
  • Calcium
  • Norepinephrine