EFFECTS OF METHYLGUANIDINE ON THE ELECTRICAL ACTIVITY OF SINGLE PACEMAKER FIBERS IN THE SINUS NODE OF THE RABBIT

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The action of methylguanidine has been studied on the pacemaker fibers in the sinus node of isolated atria from rabbits. This substance altered the atrial rate principally by affecting two parameters of the membrane potentials of the nodal fibers. It increased the rate of development (slope) of the pacemaker potential, and it increased the duration of the action potential. The former action accelerated the rate while the latter opposed the acceleration. The rate change elicited by methylguanidine depended upon the relative predominance of each of these actions. Pretreatment of the rabbits with reserpine plus the presence of propranolol abolished the increase in slope of the pacemaker potential; hence, this action of methylguanidine is presumably due to the release of endogenous norepinephrine. Reserpine pretreatment or propranolol had no effect on the increase in duration of the action potential. This action is probably a direct effect of methylguanidine, per se. Methylguanidine appears to behave like an indirectly-acting sympathomimetic amine.