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 and LTMs, 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 subgroups were 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 pA pF^-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 I_h expression and/or properties (e.g. in chronic/pathological pain states) may influence both nociceptor and LTM excitability.