The role of membrane depolarization in norepinephrine-induced contractions of the rabbit mesenteric resistance artery.
Changes in membrane potential during norepinephrine-induced contractions in the rabbit mesenteric resistance artery (3rd or 4th branch) were investigated using microelectrodes. Norepinephrine at concentrations greater than 10(-6) M depolarized the membrane and induced contractions dose-dependently. Maximum effects were produced by 10(-4) M norepinephrine. Depolarization was maintained at almost steady level during 15 min application of norepinephrine. During the same period, contractions continued with slight decay. Oscillatory contractions were observed at more than 3 X 10(-6) M norepinephrine, and occasionally persisted throughout the application of norepinephrine. Treatments with Ca2+-rich 1 mM EGTA solution, 10(-5) M diltiazem, 3 X 10(-6) M D600 and 1 mM La3+ did not significantly affect the amount of depolarization induced by 10(-4) M norepinephrine; however, contractions were greatly inhibited by these treatments. Replacement of Na+ by choline markedly reduced depolarization while contractions were not affected. In Ca2+ -free Na+-free solution, no depolarization was induced, while contractions were still produced by norepinephrine, indicating that Cl- was not essential for membrane depolarization. These results suggest that contractions of the rabbit mesenteric resistance artery to norepinephrine are mainly due to the enhanced influx of extracellular Ca2+ which is not dependent on potential-sensitive mechanisms. Depolarization is thought to be due to the increase in the membrane permeability to Na+ and Cl- which is coincidentally produced by norepinephrine. The membrane potential oscillations were dependent on Ca entry but could not be shown to be the result of fluctuations in Ca current.
D000818:Animals; D002118:Calcium / Q000502:physiology; D004110:Diltiazem / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits
D004110:Diltiazem; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine