Mechanism of barium-induced contraction in the vascular smooth muscle of rabbit aorta.
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.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D001464:Barium / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D014700:Verapamil / Q000494:pharmacology
D007473:Ion Channels; D001464:Barium; D007811:Lanthanum; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D009543:Nifedipine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine