Expression and properties of hyperpolarization-activated current (Ih) in vivo in rat DRG neurons with known sensory functions

I(h) has been implicated in nociception/pain, but its expression levels in nociceptors remained unknown. We recorded I(h) magnitude and properties by voltage clamp from dorsal root ganglion (DRG) neurons in vivo, after classifying them as nociceptive or low-threshold-mechanoreceptors (LTMs) and as having C-, Aδ- or Aα/β-conduction velocities (CVs). For both nociceptors and LTMs, I(h) amplitude and I(h) density (at -100mV) were significantly positively-correlated with CV. Median I(h) magnitudes and I(h) density in neuronal subgroups were respectively: muscle spindle afferents (MSAs): -4.6nA, -33pA/pF; cutaneous Aα/β LTMs: -2.2nA, -20pA/pF; Aβ-nociceptors: -2.6nA, -21pA/pF; both Aδ-LTMs and nociceptors: -1.3nA, ~-14pA/pF; C-LTMs: -0.4nA, -7.6pA/pF and C-nociceptors: -0.26nA, -5pA/pF. I(h) activation slow time constants (slow taus) were strongly correlated with fast taus; both were shortest in MSAs. Most neurons had taus consistent with HCN1-related I(h); others had taus closer to HCN1+HCN2 channels, or HCN2 in presence of cAMP. In contrast, median half-activation voltages (V(0.5)) of -80 to -86mV for neuronal subgroups suggest contributions of HCN2 to I(h). Taus were unrelated to CV but were inversely correlated with I(h) and I(h) density for all non-MSA LTMs, and for Aδ-nociceptors. From activation curves ~2-7% of I(h) would be activated at normal membrane potentials. The high I(h) may be important for excitability of A-nociceptors (responsible for sharp/pricking-type pain) and Aα/β-LTMs (tactile sensations and proprioception). Underlying HCN expression in these subgroups therefore needs to be determined. Altered I(h) expression and/or properties (e.g. in chronic/pathological pain states), may influence both nociceptor and LTM excitability.