IRP3: KCNQ (Kv7) channel turnover and cellular excitability

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KCNQ (Kv7) genes encode ct-subunits of voltage-gated potassium (Kv) channels. Kv7 channels may activate and slowly deactivate at negative membrane potentials, i.e. in the subthreshold potential-range of action-potential firing. Kv7 channels, therefore, may be major players in controlling membrane resting potentials and/or action potential firing frequencies in excitable cells. Mutations in KCNQ genes may be associated with channelopathies such as the long QT syndrome (LQTS), BFNC, a benignƒorm of neonatal convulsions, or deafness. Many of the disease-related mutations affect apparently Kv7 channel trafficking. A hallmark of Kv7 channels is their tight association with calmodulin. The binding of calmodulin to C-terminal domain(s) of Kv7 subunit appears essential for assembly and trafficking of active Kv7 channels to the plasma membrane. Mutations in the Kv7 calmodulin binding site that are associated with LQTS or BFNC cause in vitro a reduced number of active Kv7 channels in the plasma membrane. Based on previous studies we hypothesize that stimulation of Gαq/11-coupled receptors modulates Kv7 channel turnover associated with short- and long-term changes in neuronal excitability.