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

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.