Ineffectiveness of organic calcium channel blockers in antagonizing long-term potentiation

Jeffrey S. Taube, Philip A Schwartzkroin

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Evidence has accumulated suggesting that the presence of calcium is critical for development of hippocampal long-term potentiation (LTP). However, there is a paucity of information about whether calcium's role in LTP is pre- or postsynaptic. In the present study, we examined the effectiveness of nitrendipine, verapamil, flunarizine and the benzodiazepine diazepam in: (1) blocking voltage-dependent calcium channels; (2) blocking synaptic transmission; and (3) preventing development of LTP. Using the in vitro slice preparation, we obtained intracellular and extracellular recordings from guinea pig hippocampal CA1 pyramidal cells. At the cellular level, all 4 drugs were ineffective in blocking voltage-dependent calcium spikes (TTX resistant) and the calcium-dependent afterhyperpolarization. Verapamil and diazepam appeared to antagonize synaptic transmission, as reflected in smaller population spike amplitudes. Development of long-term potentiation was not affected by the presence of verapamil, flunarizine and diazepam. Nitrendipine appeared to reduce the percentage of slices exhibiting LTP; however, ethanol, the vehicle used to dissolve nitrendipine, was shown in separate experiments to reduce the percentage of slices exhibiting LTP. These results suggest that neither the organic calcium channel blockers - nitrendipine, verapamil, and flunarizine - nor micromolar concentrations of diazepam are potent blockers of extrasynaptic voltage-sensitive calcium channels in hippocampus. They thus cannot be used to demonstrate a specific pre- or postsynaptic calcium role in LTP.

Original languageEnglish (US)
Pages (from-to)275-285
Number of pages11
JournalBrain Research
Volume379
Issue number2
DOIs
StatePublished - Aug 6 1986
Externally publishedYes

Keywords

  • calcium channel blocker
  • hippocampal slice
  • long-term potentiation

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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