Phenytoin action on the excitable membrane of mouse neuroblastoma

J. B. Tuttle, E. Richelson

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The effect of the anticonvulsant and antiarrhythmic drug, phenytoin (diphenylhydantoin, DPH), upon the passive and active membrane properties of aminopterin-treated mouse neuroblastoma cells (clone N1E-115) was examined by intracellular recording during constant-flow superfusion. This agent was previously found to be unique, when compared to other anticonvulsants, in its abiliy to reverse the ionic excitation of neuroblastoma cells. In the present work, DPH (40 μM) had an inhibitory effect which was greatest upon Ca++-dependent components of the action potential of these cells. These include a tetrodotoxin-insensitive action potential and positive after-potential, both of which are also inhibited in the absence of extracellular Ca++. Furthermore, DP prevented the potentiation of both of these responses caused by repetitive stimulation. The drug was also found to alter the passive membrane properties of these cells, causing a 30% reduction in resting input resistance and a slight depolarization of the resting transmembrane potential. However, DPH did not detectably alter either the permeability ratio of the membrane to Na+ and K+ [P(Na)/P(K)] or the intracellular concentration of K+, as estimated from plots of membrane potential vs. extracellular K+. Nonetheless, the drug reduced the sensitivity of the resting membrane to small changes in extracellular potassium concentration. Thus, the actions of DPH upon the neuroblastoma membrane may have some relevance to its clinical effectiveness, making neuroblastoma a useful preparation to further examine the mode of action of this anticonvulsant.

Original languageEnglish (US)
Pages (from-to)632-637
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume211
Issue number3
StatePublished - 1979
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology

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