Accommodation to hyperpolarizing currents: differences between motor and sensory nerves in mice.

Peripheral motor nerves have revealed variability in excitability by hyperpolarizing current at specific target response levels, likely reflecting differences in the hyperpolarization-activated current (Ih). Whether such variability in Ih exists in sensory axons is yet to be established. We performed nerve excitability testing in mouse tail motor and sensory nerves at 3 target response levels (20, 40, and 60% of the maximum amplitudes). Target-level dependent variability was present by long hyperpolarizing currents in motor and sensory nerves in which the recording at the low target level showed smaller threshold changes than at the high target level. Other excitability measures, however, showed no variability. Furthermore, the accommodation by long, strong hyperpolarization revealed smaller S3 accommodation (threshold change between the maximum and at the end of the 200 ms conditioning pulse) at the low target response level in sensory axons, but not in motor axons. Variation in the kinetics of the subtypes of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in motor and sensory axons is the most likely explanation for these findings. The present study has proposed that nerve excitability testing may provide a non-invasive means for the assessment of the different types of Ih in neurological disorders where HCN subtypes play unique pathophysiological roles.