Role of auxiliary β1-, β2-, and β3-subunits and their interaction with Nav1.8 voltage-gated sodium channel

Abstract

The nociceptive C-fibers of the dorsal root ganglion express several sodium channel isoforms that associate with one or more regulatory β-subunits (β1–β4). To determine the effects of individual and combinations of the β-subunit isoforms, we co-expressed Nav1.8 in combination with these β-subunits in Xenopus oocytes. Whole-cell inward sodium currents were recorded using the two-microelectrode voltage clamp method. Our studies revealed that the co-expression β1 alone or in combination with other β-subunits enhanced current amplitudes, accelerated current decay kinetics, and negatively shifted the steady-state curves. In contrast, β2 alone and in combination with β1 altered steady-state inactivation of Nav1.8 to more depolarized potentials. Co-expression of β3 shifted steady-state inactivation to more depolarized potentials; however, combined β1β3 expression caused no shift in channel availability. The results in this study suggest that the functional behavior of Nav1.8 will vary depending on the type of β-subunit that expressed under normal and disease states.