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- W3038962142 abstract "TRPC channels are Ca2+-permeable nonselective cation channels activated downstream from phospholipase C (PLC). Although most TRPC channels can be activated by stimulating Gq/11-coupled receptors, TRPC4 requires simultaneous stimulation of Gi/o-coupled receptors, making it a perfect detector of coincident Gi/o and Gq/11 signaling. Evidence shows that activated Gαi/o proteins work together with PLCδ1 to induce robust TRPC4 activation and the process is accelerated by stimulation of other PLC isozymes, such as PLCβ through Gq/11 proteins. Mechanistically, Gq/11-PLCβ activation produces triggering proton and calcium signals to initiate self-propagating PLCδ1 activity, crucial for Gi/o-mediated TRPC4 function. Thus, TRPC4-containing channels are activated under conditions not only when coincident Gi/o and Gq/11 stimulation occurs, but also when Gi/o stimulation coincides with proton and Ca2+ signals. The resulting cytosolic Ca2+ rise and membrane depolarization switch the inhibitory Gi/o response to excitation. The conditions and implications of Gi/o-mediated TRPC4 activation in physiology and pathophysiology warrant further investigation." @default.
- W3038962142 created "2020-07-10" @default.
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- W3038962142 date "2020-10-01" @default.
- W3038962142 modified "2023-10-18" @default.
- W3038962142 title "TRPC4 as a coincident detector of Gi/o and Gq/11 signaling: mechanisms and pathophysiological implications" @default.
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- W3038962142 doi "https://doi.org/10.1016/j.cophys.2020.06.008" @default.
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