Expression and properties of hyperpolarization-activated current in rat dorsal root ganglion neurons with known sensory function

The hyperpolarization-activated current (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 andLTMs, I(h) amplitude and I(h) density (at -100 mV) were significantly positively correlated with CV.Median I(h) magnitudes and I(h) density in neuronal subgroupswere respectively:muscle spindle afferents(MSAs):-4.6 nA,-33 pA pF(-1); cutaneous Aα/β LTMs: -2.2 nA, -20 pA pF(-1); Aβ-nociceptors: -2.6 nA, -21 pA pF(-1); both Aδ-LTMs and nociceptors: -1.3 nA, ∼-14 pA pF(-1); C-LTMs: -0.4 nA, -7.6 pA pF(-1); and C-nociceptors: -0.26 nA, -5 pApF(-1). I(h) activation slow time constants (slow τ values) were strongly correlated with fast τ values; both were shortest in MSAs. Most neurons had τ values consistent with HCN1-related I(h); others had τ values closer to HCN1+HCN2 channels, or HCN2 in the presence of cAMP. In contrast, median half-activation voltages (V(0.5)) of -80 to -86 mV for neuronal subgroups suggest contributions of HCN2 to I(h). τ values 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 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 Ih expression and/or properties (e.g. in chronic/pathological pain states) may influence both nociceptor and LTM excitability.expression and/or properties (e.g. in chronic/pathological pain states) may influence both nociceptor and LTM excitability.