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

LINLIN GAO; SIMON MCMULLAN; LAICHE DJOUHRI; CRISTIAN ACOSTA; ALEXANDER HARPER; SALLY LAWSON

THE JOURNAL OF PHYSIOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2012 vol. 590 p. 4691 - 4705

0022-3751

The hyperpolarization-activated current (Ih) has been implicated in nociception/pain, but its expression levels in nociceptors remained unknown. We recorded Ih 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-, Adelta- or Aalpha/beta-conduction velocities (CVs). For both nociceptors and LTMs, Ih amplitude and Ih density (at -100 mV) were significantly positively correlated with CV. Median Ih magnitudes and Ihdensity in neuronal subgroups were respectively: muscle spindle afferents (MSAs): 4.6 nA, 33 pA/pF; cutaneous Aalpha/beta LTMs: 2.2 nA, 20 pA/pF; Abeta-nociceptors: 2.6 nA, 21 pA/pF; both Adelta-LTMs and nociceptors: 1.3 nA, 14 pA/pF; C-LTMs: 0.4 nA, 7.6 pA/pF; and C-nociceptors: 0.26 nA, 5 pA/pF. Ih activation slow time constants (slow tau values) were strongly correlated with fast tau values; both were shortest in MSAs. Most neurons had tau values consistent with HCN1-related Ih; others had tau values closer to HCN1+HCN2 channels, or HCN2 in the presence of cAMP. In contrast, median half-activation voltages (V0.5) of -80 to -86 mV for neuronal subgroups suggest contributions of HCN2 to Ih. Tau values were unrelated to CV but were inversely correlated with Ih and Ih density for all non-MSA LTMs, and for Adelta-nociceptors. From activation curves aprox. 2-7% of Ih would be activated at normal membrane potentials. The high Ih may be important for excitability of A-nociceptors (responsible for sharp/pricking-type pain) and Aalpha/beta-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.