Electrophysiological effects of bupivacaine on transitional pacemaker cells of the frog heart

The effects of bupivacaine, a long-acting local anesthetic, were studied on action potentials of spontaneously beating sinus venosus of the frog Caudiverbera caudiverbera. The study was accomplished by recording transmembrane potentials of pacemaker transitional cells. Action potentials of these cells are known to have both a fast and a slow ionic component. Bupivacaine (1 X 10(-5) M to 1 X 10(-4) M) caused a reversible negative chronotropic effect accompanied by decrease of diastolic depolarization rate and prolongation of sinus cycle length. This drug also markedly depressed rate of rise [(dV/dt)max] of action potentials. Tetrodotoxin (TTX) (1 X 10(-7) M) induced similar effects than bupivacaine. In atropine-treated sinus venosus the effect of bupivacaine on spontaneous rate of firing was less intense. However, in cells exposed to both drugs, a greater depression of (dV/dt)max and of other electrophysiological parameters such as action potential amplitude, overshoot and maximum diastolic potentials was observed. Depression of phase 4 depolarization seems difficult to be explained in view of the complex nature of the ionic currents underlying pacemaker depolarization. Reduction of (dV/dt)max caused by bupivacaine and mimicked by TTX was ascribed to blockade of sodium channels. It was concluded that bupivacaine by decreasing (dV/dt)max of transitional cells and by depressing diastolic depolarization slows down conduction of impulses arising from primary cells and that this action may contribute to its cardiac toxicity.