SIMULTANEOUS BLOCKADE OF INTRACELLULAR CALCIUM INCREASES AND OF NEURONAL EPILEPTIFORM DEPOLARIZATIONS BY VERAPAMIL

The specific L-type calcium channel blocker verapamil exerts an antiep ileptic effect on neurons. This effect is assumed to depend on the blo ckade of transmembraneous calcium flux during epileptic discharges. In order to test this hypothesis, fura-dextran loaded snail neurons were rendered epileptic by pentylenetetrazole (40 mmol/l). The effect of v erapamil (20 or 40 mu mol/l) on free intracellular calcium ([Ca2+](i)) transients was investigated by means of fluorescence ratio-imaging an d simultaneous intracellular membrane potential recording. During epil eptic depolarization [Ca2+](i) increased especially in the outermost s ubmembraneous areas of the neuron. [Ca2+](i) reached peak values 6-22 s after the onset of epileptic depolarizations. Application of verapam il progressively shortened the epileptic depolarizations. This shorten ing of epileptic depolarizations developed along with a diminution of the submembraneous calcium signals down to noise level. The effect was found to be reversible. It is concluded that the antiepileptic effect of verapamil depends largely on its ability to block transmembraneous calcium flux.