Mutation of serine 1506 in the sodium channel abolishes its response to protein kinase C activation, indicating this phosphorylation site is required for modulation of electrical activity.
Identifies serine 1506 as the critical phosphorylation site required for protein kinase C-mediated modulation of voltage-gated sodium channels.
Voltage-gated sodium channels are responsible for generation of action potentials in excitable cells. Activation of protein kinase C slows inactivation of sodium channels and reduces peak sodium currents. Phosphorylation of a single residue, serine 1506, that is located in the conserved intracellular loop between domains III and IV and is involved in inactivation of the sodium channel, is required for both modulatory effects. Mutant sodium channels lacking this phosphorylation site have normal functional properties in unstimulated cells but do not respond to activation of protein kinase C. Phosphorylation of this conserved site in sodium channel alpha subunits may regulate electrical activity in a wide range of excitable cells.
West et al. (1991) studied this question. Mutation of serine 1506 in sodium channel alpha subunits vs. Wild-type sodium channels was evaluated on Modulation of sodium channel inactivation and peak sodium currents by protein kinase C. Mutation of serine 1506 in the sodium channel abolishes its response to protein kinase C activation, indicating this phosphorylation site is required for modulation of electrical activity.
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