Membrane depolarization combined with Gq-activated G-protein-coupled receptors induce transient receptor potential channel 1 (TRPC1)- dependent potentiation of catecholamine release

M. Marom, L. Birnbaumer, D. Atlas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Agonists of the G q/11-activated G-protein-coupled receptors (GPCRs) combined with strong membrane depolarization (high KCl) induce a synergistic amplification of transmitter release. The molecular basis for the synergy is unknown. Here, we investigated this potentiated transmitter release (PTR) phenomenon at the single cell level by monitoring catecholamine (CA) release in chromaffin cells using amperometry. We found that the 60 mM KCl (K60)-triggered release in bovine chromaffin cells synergizes with bradykinin (BK) or histamine (Hist) to potentiate CA release. PTR was independent of Ca 2+ influx through voltage-gated calcium channels (VGCC), but required Ca 2+ at the extracellular medium and was abolished by inhibitors of phospholipase Cβ (PLCβ). The ~ four-fold PTR induced in mouse chromaffin cells by BK and K60, was not observed in chromaffin cells prepared from TRPC1 KO mice and was restored by expressing hTRPC1. The synergy between strong voltage perturbation (K60) in the presence of VGCC blockers, and the activation of the G q/11-PLCβ signal-transduction cascade generates unique and fundamental amplified signaling machinery. The concerted activation of two independent cellular pathways could reinforce physiological signals that impinge on regulation of secretory events during repeated sequence of high-frequency excitation, hyperpolarization, and relief of inhibition such as long-term potentiation (LTP), that lead to neuronal synaptic plasticity.

Original languageEnglish
Pages (from-to)132-145
Number of pages14
JournalNeuroscience
Volume189
DOIs
StatePublished - 25 Aug 2011

Keywords

  • Ca channel
  • Depolarization-evoked secretion
  • Gq/11 GPCR
  • LTP
  • PLCβ
  • TRPC channel

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