A functional assay to measure postsynaptic γ-aminobutyric acid(B) responses in cultured spinal cord neurons: Heterologous regulation of the same K+ channel

G. L. Kamatchi, M. K. Ticku

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The stimulation of postsynaptic γ-aminobutyric acid (GABA)(B) receptors leads to slow inhibitory postsynaptic potentials due to the influx of K+-ions. This was studied biochemically, in vitro in mammalian cultured spinal cord neurons by using 86Rb as a substitute for K+. (-)-Baclofen, a GABA(B) receptor agonist, produced a concentration-dependent increase in the 86Rb-influx. This effect was stereospecific and blocked by GABA(B) receptor antagonists like CGP 35 348 (3-aminopropyl-diethoxymethylphosphonic acid) and phaclofen. Apart from the GABA(B) receptors, both adenosine via adenosine1 receptors and 5-hydroxytryptamine (5-HT) via 5-HT(1α) agonists also increased the 86Rb-influx. These agonists failed to show any additivity between them when they were combined in their maximal concentration. In addition, their effect was antagonized specifically by their respective antagonists without influencing the others. These findings suggest the presence of GABA(B), adenosine1 and 5-HT(1α) receptors in the cultured spinal cord neurons, which exhibit a heterologous regulation of the same K+-channel. The effect of these agonists were antagonized by phorbol 12,13-didecanoate, an activator of protein kinase C, and pretreatment with pertussis toxin. This suggests that these agonists by acting on their own receptors converge on the same K+-channel through the G(i)/G(o) proteins. In summary, we have developed a biochemical functional assay for studying and characterizing GABA(B) synaptic pharmacology in vitro, using spinal cord neurons.

Original languageEnglish (US)
Pages (from-to)426-431
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume256
Issue number2
StatePublished - 1991
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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