SMOOTH MUSCLE RELAXANTS: DISSOCIATION BETWEEN RESTING MEMBRANE POTENTIAL AND RESTING TENSION IN RAT MYOMETRIUM

The effects of epinephrine, norepinephrine and isoproterenol were compared with those of nitroglycerin, papaverine and tetracaine on isolated rat myometrium. At concentrations between 10-7 and 10-6 M all three catecholamines completely abolished spontaneous motility. This action was accompanied by hyperpolarization of the cell membrane and reduction of resting tension. The inhibition of motility and the hyperpolarization were correlated to the extent that both were beta adrenergic effects (as shown by studies with adrenergic blocking agents). However, smaller concentrations of epinephrine (2 x 10-6 M), which reduced but did not abolish spontaneous contractions, did not alter the resting membrane potential ( RMP ). Furthermore, in concentrations which completely inhibited spontaneous motility, nitroglycerin caused only a slight hyperpolarization, and papaverine and tetracaine had no effect on RMP . Thus, hyperpolarization is not a prerequisite for inhibition of motility by these drugs. The possibility was considered that the hyperpolarization observed with higher concentrations of the catecholamines might be related to the fall in resting tension caused by the catecholamines (as distinguished from the cessation of spontaneous activity, which may or may not be accompanied by a fall incresting tension). It was also possible that the hyperpolarization was a result rather than a cause of the fall in tension. That this is not the case was shown by the finding that papaverine, even in concentrations which significantly decreased resting tension, had no effect on RMP . The addition of epinephrine to muscles already depressed by papaverine caused a marked hyperpolarization, although no further fall in resting tension could be observed. Muscles which were depolarized by high potassium solutions could still be relaxed by epinephrine, although the membrane potential was not altered by the drug under these conditions. Thus, it appears that in this tissue RMP and resting tension are not necessarily related. It was concluded that hyperpolarization is neither necessary nor responsible for the relaxant effects of the drugs tested in this study. However, the present experiments do not exclude the possibility that the hyperpolarization produced by the catecholamines may reinforce the depressant effects of these drugs on the mechanical activity of the rat uterus.