Ashton, David;
Reid, Kenneth;
Willems, Roland;
Marrannes, Roger;
Wauquier, Albert
Comparative action of flunarizine, phenytoin, carbamazepine and two calcium‐entry blockers on spontaneous epileptiforrn bursts in the low calcium‐hippocampal slice preparation
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Media type:
E-Article
Title:
Comparative action of flunarizine, phenytoin, carbamazepine and two calcium‐entry blockers on spontaneous epileptiforrn bursts in the low calcium‐hippocampal slice preparation
Description:
<jats:title>Abstract</jats:title><jats:p>Exposure of hippocampal slices to a medium containing a low Ca<jats:sup>2+</jats:sup>‐concentration and an increased concentration of Mg<jats:sup>2+</jats:sup> and K<jats:sup>+</jats:sup> resulted in the blockade of synaptic transmission and the development of spontaneous synchronized epileptiform bursts (SSEB) in area CA1. The SSEBs were measured extracellularly as a negative potential shift with superimposed population spikes. Flunarizine is a “Ca<jats:sup>2+</jats:sup>‐entry blocker” with antiepileptic actions in humans. We compared flunarizine with two reference antiepileptics (phenytoin and carbamazepine) and two other “Ca<jats:sup>2+</jats:sup>‐entry blockers” (verapamil and nimodipine) for their ability to reduce SSEBs. Flunarizine, which is insoluble in ACSF bathing medium, was applied in a nanodrop directly onto the CA1 region of the slice. All other drugs were applied in the bathing medium. Flunarizine (1 picomol), phenytoin (2 × 10<jats:sup>−5</jats:sup> M), and carbamazepine (5 × 10<jats:sup>−6</jats:sup>, 5 × 10<jats:sup>−5</jats:sup> M) reduced the SSEBs. Nimodipine (1 × 10<jats:sup>−5</jats:sup> M) and verapamil (2 × 10<jats:sup>−5</jats:sup>M) were ineffective. Increases in extracellular K<jats:sup>+</jats:sup> occurred synchronously with, and decreases in extracellular Ca<jats:sup>2+</jats:sup> followed, negative potential deflections during SSEBs. As the amplitude of potential shifts decreased after flunarizine so did the ion‐shifts. Since changes in Ca<jats:sup>2+</jats:sup> and K<jats:sup>+</jats:sup> did not occur before changes in potential, modulation of Ca<jats:sup>2+</jats:sup> or K<jats:sup>+</jats:sup> channels in striatum pyrarnidale is unlikely to explain flunarizine's ability to reduce synchronized bursts. Further, the ability to block Ca<jats:sup>2+</jats:sup> channels in the periphery appears to be unrelated to the ability to block SSEBs in this model. It is suggested that reduction of Na<jats:sup>+</jats:sup> currents during depolarization may be the basis of the similar effects of phenytoin, carbamazepine and flunarizine in this model.</jats:p>