Premium
Expression and properties of hyperpolarization‐activated current in rat dorsal root ganglion neurons with known sensory function
Author(s) -
Gao L. L.,
McMullan S.,
Djouhri L.,
Acosta C.,
Harper A. A.,
Lawson S. N.
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2012.238485
Subject(s) - nociceptor , dorsal root ganglion , neuroscience , sensory system , hyperpolarization (physics) , nociception , sensory neuron , electrophysiology , chemistry , anatomy , current clamp , patch clamp , biology , receptor , biochemistry , nuclear magnetic resonance spectroscopy , organic chemistry
Key point• Ih is a hyperpolarisation‐activated current that influences neuronal excitability and is present in some sensory neurons. • The magnitude and properties of I h in different groups of sensory neurons that respond to painful stimuli (nociceptors) or to non‐painful stimuli, such as low threshold mechanoreceptors (LTMs), were unknown. • We found that neurons with the greatest I h were the nociceptors and LTMs with the fastest conducting fibres. The highest I h of all was present in LTM neurons that sense muscle stretch and length (muscle spindle afferents). • The high levels of I h could fundamentally influence excitability of fast conducting sensory neurons which detect muscle stretch/length, touch and pressure, and painful stimuli. I h could thus influence sensations associated with all these. • The properties of I h are similar to those of HCN1‐ and HCN2‐related I h , suggesting that these channels underlie the current.Abstract 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.