Gating properties of Nav1.7 and Nav1.8 peripheral nerve sodium channels

Abstract

Several distinct components of voltage-gated sodium current have been recorded from native dorsal root ganglion (DRG) neurons that display differences in gating and pharmacology. This study compares the electrophysiological properties of two peripheral nerve sodium channels that are expressed selectively in DRG neurons (Nav1.7 and Nav1.8). Recombinant Nav1.7 and Nav1.8 sodium channels were coexpressed with the auxiliary β1 subunit in Xenopus oocytes. In this system coexpression of the β1 subunit with Nav1.7 and Nav1.8 channels results in more rapid inactivation, a shift in midpoints of steadystate activation and inactivation to more hyperpolarizing potentials, and an acceleration of recovery from inactivation. The coinjection of β1 subunit also significantly increases the expression of Nav1.8 by sixfold but has no effect on the expression of Nav1.7. In addition, a great percentage of Nav1.8+β1 channels is observed to enter rapidly into the slow inactivated states, in contrast to Nav1.7+β1 channels. Consequently, the rapid entry into slow inactivation is believed to cause a frequency-dependent reduction of Nav1.8+β1 channel amplitudes, seen during repetitive pulsing between 1 and 2 Hz. However, at higher frequencies (>20 Hz) Nav1.8+β1 channels reach a steady state to ∼42% of total current. The presence of this steady-state sodium channel activity, coupled with the high activation threshold (V0.5 = -3.3 mV) of Nav1.8+β1, could enable the nociceptive fibers to fire spontaneously after nerve injury.