The negative inotropic action of propanidid. influence on calcium movements in atrial tissue.

Propanidid (Epontol), a general anaesthetic agent with a particularly short action in vivo significantly depressed the contraction amplitude of guinea pig isolated atria. A steep concentration-response curve could be established. Contractile force of electrically driven atria (180/min) was reduced by approximately 50% at a propanidid concentration of 3.5 x 10-4 M in the medium. The negative inotropic effect developed rapidly (less than 10 min). At concentrations of 4.5 x 10-4 M and less propanidid hardly reduced the frequency of spontaneously beating atria. The uptake of extracellular 45 Ca by spontaneously beating atria occurred significantly more slowly in presence of propanidid (4.5 x 10-4 M ), whereas the exchangeable calcium fraction remained unchanged. Accordingly, propanidid reduced the rate of exchange of calcium so that less ionized calcium was available for excitation-contraction coupling. Propanidid (4.5 x 10-4 M) accelerated the uptake of 45Ca by isolated plasma membranes, obtained from guinea pig ventricular muscle. Moreover, the binding capacity for calcium by isolated membranes was increased in presence of propanidid. These observations imply that less ionized calcium is available for activation of the contractile system. It is concluded that the negative inotropic action of propanidid is probably due to the drug's influence on membrane function, thus bringing about an important change in cellular calcium metabolism.