Simultaneous blockade of intracellular calcium increases and of neuronal epileptiform depolarizations by verapamil.
The specific L-type calcium channel blocker verapamil exerts an antiepileptic effect on neurons. This effect is assumed to depend on the blockade 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 verapamil (20 or 40 mumol/l) on free intracellular calcium ([Ca2+]i) transients was investigated by means of fluorescence ratio-imaging and simultaneous intracellular membrane potential recording. During epileptic depolarization [Ca2+]i increased especially in the outermost submembraneous areas of the neuron. [Ca2+]i reached peak values 6-22 s after the onset of epileptic depolarizations. Application of verapamil progressively shortened the epileptic depolarizations. This shortening 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.
Institut für Experimentelle Epilepsieforschung, Universität Münster, Germany.
M
M
Wiemann
D
D
Jones
H
H
Straub
U
U
Altrup
E J
EJ
Speckmann
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004594:Electrophysiology; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D006372:Helix, Snails; D007425:Intracellular Membranes / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010433:Pentylenetetrazole; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014700:Verapamil; D002118:Calcium; D010433:Pentylenetetrazole