The hypothesis that an alteration in resting membrane potential (E(m)) is responsible for postjunctional supersensitivity in vascular muscle was tested in the rabbit saphenous artery. Rabbits were treated with reserpine (0.3 mg/g/day i.p.) for 1, 3 or 7 days. Saphenous arteries were then removed for measurement of E(m), contraction or norepinephrine content. Norepinephrine content was reduced by 94% 24 hr after the first dose of reserpine and remained at that level with longer treatment periods. A nonspecific postjunctional supersensitivity to various agonists (norepinephrine, methoxamine, histamine and potassium) associated with a 4 to 5 mV depolarization of the vascular muscle cells was found in saphenous arteries only from 3-day reserpine-treated animals. The time course of the increased sensitivity and the depolarization were the same. The threshold potential for potassium contraction was the same in control and supersensitive arteries. Therefore, a lower concentration of a depolarizing agonist will produce contraction in supersensitive arteries since the E(m) is closer to the threshold for contraction. Acute procedures (double the normal extra-cellular concentration of potassium or 3 x 10 -6 M ouabain) also caused depolarization and postjunctional supersensitivity in control arteries. Ouabain did not depolarize or change the sensitivity of arteries from rabbits pretreated with reserpine for 3 days. Depolarized arteries (71 mM K +) from animals pretreated for 3 days were also more sensitive to calcium. It is concluded that a partial depolarization contributes to supersensitivity. The fact that ouabain has no effect on supersensitive arteries suggests that chronic depression of neurotransmission and ouabain cause depolarization by a common mechanism, probably a depression of electrogenic Na +, K + pumping. However, membrane depolarization is not the only mechanism contributing to postjunctional supersensitivity since there is a membrane-potential-independent supersensitivity to calcium ions.
|Number of pages||10|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|Publication status||Published - 1981|
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