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Functional impact of the hyperpolarization‐activated current on the excitability of myelinated A‐type vagal afferent neurons in the rat
Author(s) -
Zhou YuHong,
Sun LiHua,
Liu ZhenHong,
Bu Guixue,
Pang XiaoPing,
Sun ShiChao,
Qiao GuoFen,
Li BaiYan,
Schild John H
Publication year - 2010
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2010.05396.x
Subject(s) - hyperpolarization (physics) , depolarization , current clamp , membrane potential , excitatory postsynaptic potential , chemistry , biophysics , neuroscience , voltage clamp , electrophysiology , biology , inhibitory postsynaptic potential , nuclear magnetic resonance spectroscopy , organic chemistry
Summary 1. The hyperpolarization‐induced, cation‐selective current I h is widely observed in peripheral sensory neurons of the vagal and dorsal root ganglia, but the peak magnitude and voltage‐ and time‐dependent properties of this current vary widely across afferent fibre type. 2. Using patch clamp investigations of rat isolated vagal ganglion neurons (VGN) identified as myelinated A‐type afferents, we established a compendium of functional correlates between changes in membrane potential and the dynamic discharge properties of these sensory neurons as a result of the controlled recruitment of I h using the current clamp technique. 3. Two robust reponses were observed in response to hyperpolarizing step currents: (i) upon initiation of the negative step current, there was a rapid hyperpolarization of membrane potential followed by a depolarizing voltage sag (DVS) towards a plateau in membrane potential as a result of steady state recruitment of I h ; and (ii) upon termination of the negative step current, there was a rapid return to the pretest resting membrane potential that often led to spontaneous action potential discharge. These data were strongly correlated ( r 2 > 0.9) with a broad compendium of dynamic discharge characteristics in these A‐type VGN. 4. In response to depolarizing step currents of increasing magnitude, the discharge frequency of the A‐type VGN responded with increases in the rate of sustained repetitive discharge. Upon termination of the depolarizing step current, there was a post‐excitatory membrane hyperpolarization of a magnitude that was strongly correlated with action potential discharge rate ( r 2 > 0.9). 5. Application of the selective hyperpolarization‐activated cyclic nucleotide gated (HCN) channel blockers ZD7288 (10 μmol/L) or CsCl (1.0 mmol/L) abolished I h and all of the aforementioned functional correlates. In addition to reducing the excitability of the A‐type VGN to step depolarizing currents. 6. Because there is increasing evidence that the HCN channel current may represent a valid target for pharmacological intervention, the quantitative relationships described in the present study could potentially help guide the molecular and/or chemical modification of HCN channel gating properties to effect a particular outcome in VGN discharge properties, ideally well beyond merely selective blockade of a particular HCN channel subtype.