Muscarinic m3 receptors and dynamics of intracellular Ca2+ cerebellar granule neurons

Edward B. Fohrman, Gabriel de Erausquin, Erminio Costa, Walter J. Wojcik

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Activation of muscarinic receptors with carbachol has no effect on intracellular Ca2+ concentration in cerebellar granule cell cultures. Only after elevating intracellular Ca2+ concentrations using either 40 mM KCl or activating glutamatergic receptors was carbachol able to increase intracellular Ca2+. The response lasted about 10 s, and the median increase in intracellular Ca2+ with either 100 μM or 300 μM carbachol was about 85 nM. Carbachol at 30 μM elicited an increase in intracellular calcium that was half maximal. After a 16 min or 32 min delay following cell depolarization, responses to carbachol were only found in about 20% of the cells studied and the median increase in intracellular Ca2+ was about 14 nM. (-)-Quinuclidinylxanthene-9-carboxylate hemioxalate (QNX) at 10 nM (a muscarinic m3 antagonist), but not methoctramine at 5 μM (a muscarinic m2 antagonist), attenuated the action of 100 μM carbachol. This carbachol-mediated response was elicited in the absence of extracellular Ca2+ and in the presence of 10 μM dantrolene, but was blocked by 1 μM thapsigargin. Lastly, treatments of cerebellar granule cell cultures with carbachol (100 μM) for up to 12 h results in a desensitization of the carbachol-mediated release of stored Ca2+. Thus, carbachol acts on muscarinic m3 receptors to induce the release of Ca2+ from IP3-sensitive Ca2+ stores that must be filled by a prior period of high intracellular Ca2+.

Original languageEnglish (US)
Pages (from-to)263-271
Number of pages9
JournalEuropean Journal of Pharmacology: Molecular Pharmacology
Volume245
Issue number3
DOIs
StatePublished - May 15 1993
Externally publishedYes

Keywords

  • Caffeine-sensitive Ca store
  • Fluorescence microscopy of intracellular Ca
  • Fura-2 fluorescence
  • IP-sensitive Ca store
  • Muscarinic receptor
  • Neurotransmitter receptor desensitization

ASJC Scopus subject areas

  • Pharmacology

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