title: Membrane depolarization combined with Gq-activated G-protein-coupled receptors induce transient receptor potential channel 1 (TRPC1)- dependent potentiation of catecholamine release.
abstract: Agonists of the Gq/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 Ca2+ influx through voltage-gated calcium channels (VGCC), but required Ca2+ 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 Gq/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.
authors.affiliation: Department of Biological Chemistry, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Marom
authors.forename: L
authors.initials: L
authors.lastname: Birnbaumer
authors.forename: D
authors.initials: D
authors.lastname: Atlas
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism*; D004789:Enzyme Activation; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology; D015640:Ion Channel Gating; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D009543:Nifedipine / Q000494:pharmacology; D054799:Phospholipase C beta / Q000502:physiology; D043782:Receptor, Bradykinin B2 / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D011969:Receptors, Histamine H1 / Q000502:physiology; D015398:Signal Transduction; D013045:Species Specificity; D050052:TRPC Cation Channels / Q000235:genetics / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002395:Catecholamines; D043782:Receptor, Bradykinin B2; D043562:Receptors, G-Protein-Coupled; D011969:Receptors, Histamine H1; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D006632:Histamine; D054799:Phospholipase C beta; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D009543:Nifedipine; D001920:Bradykinin; D002118:Calcium