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

Carla G. Cardenas, Lucinda P. Del Mar, Alexander V. Vysokanov, Peter B. Arnold, Luz M. Cardenas, D. James Surmeier, Reese S. Scroggs*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

1. The effect of serotonin (5-HT) on the hyperpolarization-activated cation current (I(H)) 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 I(H) 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 I(H) 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 I(H) by + 6 mV without changing peak conductance. The effects of 5-HT on I(H) 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 I(H). 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 I(H) to more depolarized potentials and increases neuronal excitability.

Original languageEnglish (US)
Pages (from-to)507-523
Number of pages17
JournalJournal of Physiology
Volume518
Issue number2
DOIs
StatePublished - Jul 15 1999

ASJC Scopus subject areas

  • Physiology

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