MEMBRANE DEPOLARIZATION COMBINED WITH Gq-ACTIVATED G-PROTEIN-COUPLED RECEPTORS INDUCE TRANSIENT RECEPTOR POTENTIAL CHANNEL 1 (TRPC1)- DEPENDENT POTENTIATION OF CATECHOLAMINE RELEASE

Agonists of the G(q/11)-activated G-protein-coupled receptors (GPCRs) combined with strong membrane depolarization (high KCI) 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 KCI (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 C beta (PLC beta). The similar to 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)-PLC beta 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. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.