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.
Model Type: Neuron or other electrically excitable cell
Currents: I M
Receptors: Muscarinic; Cholinergic Receptors
Model Concept(s): Ion Channel Kinetics; Signaling pathways; G-protein coupled
Simulation Environment: Virtual Cell (web link to model)
References:
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. The Journal of general physiology. 123 [PubMed]
Shapiro MS. (2004). Why biophysicists make models: quantifying modulation of the M current. The Journal of general physiology. 123 [PubMed]