Serotonergic modulation of hyperpolarization-activated current in acutely isolated rat dorsal root ganglion neurons

J Physiol. 1999 Jul 15;518 ( Pt 2)(Pt 2):507-23. doi: 10.1111/j.1469-7793.1999.0507p.x.


1. The effect of serotonin (5-HT) on the hyperpolarization-activated cation current (IH) was studied in small-, medium- and large-diameter acutely isolated rat dorsal root ganglion (DRG) cells, including cells categorized as type 1, 2, 3 and 4 based on membrane properties. 5-HT increased IH in 91 % of medium-diameter DRG cells (including type 4) and in 67 % of large-diameter DRG cells, but not other DRG cell types. 2. The increase of IH by 5-HT was antagonized by spiperone but not cyanopindolol, and was mimicked by 5-carboxyamidotryptamine, but not (+)-8-hydroxydipropylaminotetralin (8-OH-DPAT) or cyanopindolol. These data suggested the involvement of 5-HT7 receptors, which were shown to be expressed by medium-diameter DRG cells using RT-PCR analysis. 3. 5-HT shifted the conductance-voltage relationship of IH by +6 mV without changing peak conductance. The effects of 5-HT on IH were mimicked and occluded by forskolin, but not by inactive 1,9-dideoxy forskolin. 4. At holding potentials negative to -50 mV, 5-HT increased steady-state inward current and instantaneous membrane conductance (fast current). The 5-HT-induced inward current and fast current were blocked by Cs+ but not Ba2+ and reversed at -23 mV, consistent with the properties of tonically activated IH. 5. In medium-diameter neurons recorded from in the current clamp mode, 5-HT depolarized the resting membrane potential, decreased input resistance and facilitated action potential generation by anode-break excitation. 6. The above data suggest that in distinct subpopulations of DRG neurons, 5-HT increases cAMP levels via activation of 5-HT7 receptors, which shifts the voltage dependence of IH to more depolarized potentials and increases neuronal excitability.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Action Potentials / drug effects
  • Animals
  • Cell Size
  • Cyclic Nucleotide-Gated Cation Channels
  • Dopamine Antagonists / pharmacology
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism*
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • In Vitro Techniques
  • Ion Channels / drug effects
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / metabolism*
  • Neurons, Afferent / ultrastructure
  • Patch-Clamp Techniques
  • Pindolol / analogs & derivatives
  • Pindolol / pharmacology
  • Potassium Channels
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serotonin / analogs & derivatives
  • Serotonin / pharmacology*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Spiperone / pharmacology


  • Cyclic Nucleotide-Gated Cation Channels
  • Dopamine Antagonists
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels
  • Potassium Channels
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • serotonin 7 receptor
  • Serotonin
  • cyanopindolol
  • Spiperone
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • 5-carboxamidotryptamine
  • Pindolol