Receptor-mediated modulation of KCNQ channels regulates neuronal excitability. This study concerns
the kinetics and mechanism of M1 muscarinic receptor-mediated regulation of the cloned neuronal M channel, KCNQ2/KCNQ3 (Kv7.2/Kv7.3). ... observations were successfully described by a kinetic model representing biochemical steps of the signaling
cascade using published rate constants where available. The model supports the following sequence of events for
this Gq-coupled signaling: A classical G-protein cycle, including competition for nucleotide-free G-protein by all
nucleotide forms and an activation step requiring Mg2, followed by G-protein-stimulated phospholipase C and
hydrolysis of PIP2, and finally PIP2 dissociation from binding sites for inositol lipid on the channels so that KCNQ
current was suppressed. See paper for details and more.
References:
1 .
Suh BC, Horowitz LF, Hirdes W, Mackie K, Hille B (2004) Regulation of KCNQ2/KCNQ3 current by G protein cycling: the kinetics of receptor-mediated signaling by Gq. J Gen Physiol 123:663-83 [PubMed]
2 .
Shapiro MS (2004) Why biophysicists make models: quantifying modulation of the M current. J Gen Physiol 123:657-62 [PubMed]
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