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

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‐HT 7 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 Ba 2+ 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‐HT 7 receptors, which shifts the voltage dependence of I H to more depolarized potentials and increases neuronal excitability.