Functional properties and differential neuromodulation of Na v1.6 channels

Abstract

The voltage-gated sodium channel Na v1.6 plays unique roles in the nervous system, but its functional properties and neuromodulation are not as well established as for Na V1.2 channels. We found no significant differences in voltage-dependent activation or fast inactivation between Na V1.6 and Na V1.2 channels expressed in non-excitable cells. In contrast, the voltage dependence of slow inactivation was more positive for Na v1.6 channels, they conducted substantially larger persistent sodium currents than Na v1.2 channels, and they were much less sensitive to inhibition by phosphorylation by cAMP-dependent protein kinase and protein kinase C. Resurgent sodium current, a hallmark of Na v1.6 channels in neurons, was not observed for Na V1.6 expressed alone or with the auxiliary β 4 subunit. The unique properties of Na V1.6 channels, together with the resurgent currents that they conduct in neurons, make these channels well-suited to provide the driving force for sustained repetitive firing, a crucial property of neurons.