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The effect of Cl removal on the depolarizations and contractions produced by activation of the alpha 1-adrenoceptor in the isolated rat anococcygeus was studied. In normal Krebs solution the ionophoretic application of noradrenaline and phenylephrine elicited large depolarizations; when NaCl was replaced with Na benzenesulphonate application of the agonists usually evoked no membrane response but sometimes a hyperpolarization or a biphasic membrane potential change was observed. Graded replacement of Cl by benzenesulphonate produced a progressive reduction in the depolarizing ability of noradrenaline and phenylephrine. When NaCl was replaced with Na isethionate or glucuronate, noradrenaline evoked small depolarizations in most of the cells but the sensitivity to noradrenaline (mV/nC) was reduced by over 80%. In other cells either no potential change or hyperpolarization was observed. In solutions containing low Cl the resting membrane potential was slightly depolarized by a mean value of 5-10 mV (depending on the anion substitute) and the membrane resistance was unaltered. In normal Krebs solution noradrenaline and phenylephrine evoked biphasic contractile responses but when NaCl was replaced by Na benzenesulphonate the initial rapid contraction was diminished greatly or abolished. However, the maximum tension produced by any concentration of noradrenaline was unaltered in low Cl solution although the contractions produced by phenylephrine were depressed in low Cl media. These data are further evidence that stimulation of the alpha 1-adrenoceptor in smooth muscle can produce contraction which is not mediated by a change in membrane potential.

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