Regulation of Ca++ influx into striatal neurons by kainic acid

S. N. Murphy, R. J. Miller

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

Abstract

We investigated the mechanisms by which kainic acid (KA) produces increases in [Ca++](i) in single striatal neurons in vitro using fura-2-based microfluorimetry. When neurons were depolarized by perfusion with high K+ or veratridine containing solutions, [Ca++](i) rose rapidly to a peak and then declined to a lower sustained plateau that persisted as long as the depolarizing stimulus. The peak high K+-induced rise in [Ca++](i) occurred at [K+](o) > 50 mM and the plateau was largest at 30 mM K+. [K+](o) that was > 70 mM caused the magnitude of the plateau to decrease. Responses to high K+ stimulation were completely dependent on [Ca++](o) and presumably represented Ca++ influx. Nitrendipine partially blocked the peak of the high K+-induced response and completely blocked the sustained plateau Ca++ influx. The nitrendipine-resistant portion of the high K+ response could be completely blocked by predepolarization of the cell in Ca++-free solution. KA also produced large increases in [Ca++](i) that were abolished on removal of external Ca++. Predepolarization/nitrendipine greatly reduced the effect of lower [KA] (100 μM). However, KA-induced increases in [Ca++](i) became increasingly resistant to block of voltage-sensitive Ca++ channels as [KA] rose above 100 μM, indicating a second route of Ca++ entry that may be the KA receptor-gated ionophore. About one-half the responses to KA (100 μM) also displayed a large oscillation. [Ca++](i) rose to a peak, fell and then rose again before finally declining to a plateau level. This oscillation was abolished when all external Na+ was replaced by Li+ and may result from alterations in the buffering of [Ca++](i) as a result of KA-induced Na+ influx.

Original languageEnglish (US)
Pages (from-to)184-193
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume249
Issue number1
StatePublished - 1989

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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