Inositol triphosphate-mediated Ca2+ signals direct purinergic P2Y receptor regulation of neuronal ion channels

Oleg Zaika, Gleb P. Tolstykh, David B. Jaffe, Mark S. Shapiro

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Purinergic P2Y receptors are one of four types of Gq/11-coupled receptors in rat superior cervical ganglia (SCG) sympathetic neurons. In cultured SCG neurons, purinergic and bradykinin suppression of IM were similar in magnitude and somewhat less than that by muscarinic agonists. The effects of the P2Y receptor agonist UTP on neuronal excitability and discharge properties were studied. Under current clamp, UTP increased action potential (AP) firing in response to depolarizing current steps, depolarized the resting potential, decreased the threshold current required to fire an AP, and decreased spike-frequency adaptation. These effects were very similar to those resulting from bradykinin stimulation and not as profound as from muscarinic stimulation or full M-current blockade.Wethen examined the P2Y mechanism of action. Like bradykinin, but unlike muscarinic, purinergic stimulation induced rises in intracellular [Ca2+]i. Tests using expression of IP3"sponge" or IP3 phosphatase constructs implicated IP3 accumulation as necessary for purinergic suppression of IM. Overexpression of wild-type or dominant-negative calmodulin (CaM) implicated Ca2+/CaM in the purinergic action. Both sets of results were similar to bradykinin, and opposite to muscarinic, suppression. We also examined modulation of Ca2+ channels. As for bradykinin, purinergic stimulation did not suppress ICa, unless neuronal calcium sensor-1 (NCS-1) activity was blocked by a dominant-negative NCS-1 construct. Our results indicate that P2Y receptors modulate M-type channels in SCG cells via IP3-mediated [Ca2+]i signals in concert with CaM and not by depletion of phosphatidylinositol-4, 5-biphosphate. We group purinergic P2Y and bradykinin B2 receptors together as having a common mode of action.

Original languageEnglish (US)
Pages (from-to)8914-8926
Number of pages13
JournalJournal of Neuroscience
Volume27
Issue number33
DOIs
StatePublished - Jan 15 2007

Keywords

  • Calcium channel
  • G-protein
  • M current
  • PLC signaling
  • Patch clamp
  • Purinergic receptor
  • Sympathetic neuron

ASJC Scopus subject areas

  • Neuroscience(all)

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