A comparison of the electrophysiological actions of phentolamine with those of some other antiarrhythmic drugs on tissues isolated from the rat heart.

Glass microelectrodes were used to record transmembrane electrical activity from cells located just beneath the endocardial surface of segments from the atrial and right ventricular free walls of rat hearts during superfusion and electrical stimulation in vitro at 37 degrees C. Availability of the fast sodium channels for current flow was inferred from the maximum rate of rise of membrane potential during phase 0 of the action potential. Phentolamine mesylate (2 to 20 microM) caused a concentration-dependent block of the fast sodium channel. This was reflected in prolongation of the refractory period and slowing of recovery of excitability following the action potential, without significant change in action potential duration or resting membrane potential. Increase in the concentration of KCl in the superfusate from 5 to 10 mM depolarized the muscle and potentiated the blocking action of phentolamine. Both the depolarizing and the phentolamine-potentiating actions of KCl were counteracted by simultaneous elevation of the concentration of CaCl2 in the superfusate from 2 to 10 mM. The blocking action of phentolamine was enhanced by increasing the frequency of electrical stimulation in the range 0.01 to 10 Hz. In respect of the properties listed above, lignocaine hydrochloride was similar to phentolamine but was different from quinidine sulphate in that the effects of the latter drug were not potentiated by KCl. Two other alpha-adrenoceptor antagonists, prazosin and yohimbine, both displayed actions similar to those shown by phentolamine. Tolazoline was only weakly active and dihydroergotamine (60 microM) was inactive. Dibenamine and phenoxybenzamine, unlike the previously named drugs, caused an irreversible block of the fast sodium channel. These blocking actions of alpha-adrenoceptor antagonists were not prevented by simultaneous exposure to the alpha-adrenoceptor agonist phenylephrine (1 mm). 8 Muscle from both reserpine pretreated and non-pretreated rats responded indistinguishably to phentolamine.