Modulation of calcium currents by a metabotropic glutamate receptor involves fast and slow kinetic components in cultured hippocampal neurons

Y. Sahara, G. L. Westbrook

Research output: Contribution to journalReview article

108 Scopus citations

Abstract

The modulation of high-threshold Ca2+ currents by the selective metabotropic glutamate receptor (mGluR) agonist (1S,3R)-1-aminocyclopentane- 1,3-dicarboxylic acid (ACPD), was investigated in cultured hippocampal neurons using whole-cell voltage-clamp recording. ACPD reduced high-threshold Ca2+ currents carried by Ba2+ with an EC50 of 15.5 μM. The inhibition was reversible, voltage dependent, and blocked by L-2-amino-3- phosphonopropionic acid (1 mM) or by pretreatment with pertussis toxin. Inhibition by ACPD was greatly enhanced, and became irreversible, when the nonhydrolyzable GTP analog GTPγS was included in the whole-cell pipette. In some neurons, the Ba2+ current was inhibited by L(+)-2-amino-4- phosphonobutanoic acid (L-AP4) as well as ACPD while most cells were insensitive to L-AP4, suggesting that these agonists activate distinct receptors. The inhibition of Ca2+ currents was reduced but not eliminated in the presence of either ω-conotoxin GVIA or nifedipine, suggesting that both N- and L-type Ca2+ currents were affected. The degree and kinetics of inhibition were dependent on intracellular calcium. With [Ca](i) < 1 nM, inhibition had a fast onset (t ≃ 1-2 sec) and a rapid recovery, consistent with a membrane-delimited pathway. However, a slow component of inhibition appeared when the steady state [Ca](i) was increased to 100 nM (t onset ≃ 3 min). The slow component did not require transient Ca2+ influx or release of intracellular Ca2+. We suggest that Ca2+ channel modulation by ACPD involves either two mGluR subtypes with separate coupling mechanisms or a single mGluR that couples to both mechanisms.

Original languageEnglish (US)
Pages (from-to)3041-3050
Number of pages10
JournalJournal of Neuroscience
Volume13
Issue number7
StatePublished - Jul 21 1993

Keywords

  • G-proteins
  • L-2-amino- 4-phosphonobutanoic acid
  • calcium channels
  • hippocampus
  • metabotropic glutamate receptors
  • trans-ACPD

ASJC Scopus subject areas

  • Neuroscience(all)

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