Effects of clonixin on the electrical activity of cardiac pacemaker cells

1. The electrophysiological effects of clonixin, a non-steroidal analgesic, on cardiac pacemaker cells of spontaneously beating frog sinus venosus, were studied by intracellular recording of transmembrane potentials. 2. Results show that clonixin (Clx) between 1 x 10(-6) M and 3 x 10(-4) M, decreases the OS, APA, Vmax and frequency of primary and subsidiary cells, however pacemaker cells differ in their sensitivity to Clx. 3. At 2 x 10(-6) M, Clx completely blocked the spontaneous beating of primary cells. It is necessary to increase the Clx concentration about two orders of magnitude in order to attain a similar degree of blockade of subsidiary cells. 4. Previous or simultaneous superfusion with atropine does not modify Clx effects, thus a probable cholinergic mechanism of action for Clx is discarded. 5. When Clx concentrations were lower than 5 x 10(-4) M, their effects on both types of cells were partially reversed by a 100% increase of external calcium concentration. 6. BAY K-8644 which stimulates calcium influx through calcium L-type channels, reverted Clx effects on pacemaker cells. 7. It is suggested that Clx blocks calcium inward current which generates all or part of the upstroke of primary cells and subsidiary ones, respectively.