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• W2077457780 abstract "Norepinephrine and GABA inhibit ω-conotoxin GVIA-sensitive (N-type) calcium current in embryonic sensory neurons by separate pathways. We have investigated the mechanisms that limit the modulation of N current by varying the level of activation for a single pathway or simultaneously activating multiple pathways. Calcium currents were measured with tight-seal, whole-cell recording methods. Simultaneous application of the two transmitters at saturating concentrations produced a larger inhibition of the current than either transmitter by itself, but the maximal inhibition was not linearly additive. Maximal, direct activation of GTP-binding proteins by intracellular application of guanosine 5′-(3-O-thio)-triphosphate (GTPγS) resulted in a similar limit to the inhibition; furthermore, GTPγS did not enhance the maximal inhibition produced by co-application of transmitters. Interventions downstream in the modulatory pathway (e.g. direct activation of protein kinase C or inhibition of protein phosphatases) were also unable to alter the maximal limit for inhibition. These results suggest that transmitter-mediated inhibition is not limited by receptor number, levels of G-protein or protein kinase C activation, or degree of phosphorylation; rather, the extent of inhibition may be limited by the structural properties of the N channels themselves." @default.
• W2077457780 created "2016-06-24" @default.
• W2077457780 creator A5036965007 @default.
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• W2077457780 date "1995-03-01" @default.
• W2077457780 modified "2023-10-18" @default.
• W2077457780 title "Interaction of convergent pathways that inhibit N-type calcium currents in sensory neurons" @default.
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• W2077457780 doi "https://doi.org/10.1016/0306-4522(94)00476-l" @default.
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