I_h current stabilizes excitability in rodent DRG neurons and reverses hyperexcitability in a nociceptive neuron model of inherited neuropathic pain.

ABSTRACT: We show here that hyperpolarization-activated current (I_h ) unexpectedly acts to inhibit the activity of dorsal root ganglion (DRG) neurons expressing WT Nav1.7, the largest inward current and primary driver of DRG neuronal firing, and hyperexcitable DRG neurons expressing a gain-of-function Nav1.7 mutation that causes inherited erythromelalgia (IEM), a human genetic model of neuropathic pain. In this study we created a kinetic model of I_h and used it, in combination with dynamic-clamp, to study I_h function in DRG neurons. We show, for the first time, that I_h increases rheobase and reduces the firing probability in small DRG neurons, and demonstrate that the amplitude of subthreshold oscillations is reduced by I_h . Our results show tha

SUBMITTER: Vasylyev DV 

PROVIDER: S-EPMC10843455 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature