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

Abstract

The hyperpolarization-activated cation current (IH) is expressed differentially in various subpopulations of rat sensory neurons. For example, IH is infrequently expressed by C-and Aä-type dorsal root ganglion (DRG) neurons but is prominent in most Aá-and Aâ-type DRG neurons (Harper & Lawson, 1985a,b;Scroggs et al. 1994; Valiere & McLachlan, 1996). Since C-and Aä-type DRG neurons are typically involved in the transmission of different types of information than Aâ-and Aá-type DRG neurons, it is likely that agents which modulate IH may selectively affect certain types of sensory information. Serotonin (5_HT) has previously been shown to increase IH in rat nucleus prepositus hypoglossi neurons and in guinea-pig thalamic neurons through an increase in cAMP. However, the possibility that 5_HT may modulate IH in DRG neurons, as well as the potential mechanisms involved, have not previously been explored.In an earlier study we developed a set of criteria which appeared useful in categorizing small-and medium-diameter DRG cell bodies into four groups, types 1, 2, 3 and 4, based on capsaicin sensitivity, expression of IH, IA (a transient, 4_aminopyridine-sensitive outward K¤ current) and T_type Ca¥ current amplitude (Cardenas et al. 1995). The likelihood that these categories have some functional significance is supported by subsequent findings that 5_HT1A receptor activation selectively inhibited high-threshold Ca¥ currents in type 1 DRG cells and 5_HTÚ receptor activation selectively increased TTX-insensitive Na¤ currents in type 2 DRG cells (Cardenas et al. 1995(Cardenas et al. , 1997a. In the present study we observed that 5_HT increased IH in type 4 DRG cells and a subpopulation of large-diameter DRG cells, but not in type 1, 2, or 3 DRG cells. The 5_HT receptor involved responded to several selective 5_HT Journal of Physiology (1999) 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_HTÝ 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 Ba¥ and re...

The Endogenous Redox Agent L-Cysteine Induces T-Type Ca2+ Channel-Dependent Sensitization of a Novel Subpopulation of Rat Peripheral Nociceptors

“…In addition, T-rich cells, like most other small T-type channelcontaining DRG cells, are responsive to capsaicin (Cardenas et al, 1995;Todorovic et al, 2001) and show a hyperpolarizing response to 5-HT. In contrast, medium DRG cells with prominent T-type currents and ADPs are unresponsive to capsaicin (Cardenas et al, 1995), show depolarizing responses to 5-HT (Cardenas et al, 1999), and express a high density of HVA currents (Scroggs and Fox, 1992;Cardenas et al, 1995;Dubreuil et al, 2004). These findings also support our assertion that T-rich cells are a distinct and unique subpopulation of DRG neurons.…”

“…In larger, faster-conducting A␣-and A␤-cells, 5-HT almost exclusively elicits depolarizing effects on membrane potential (Todorovic and Anderson, 1992;Cardenas et al, 1999). In contrast, experiments using intact DRG-sciatic nerve preparations have shown that in smaller, slower-conducting A␦-and C-cells, 5-HT preferentially elicits hyperpolarizing effects on membrane potential (Todorovic and Anderson, 1992).…”

Acute p38-Mediated Modulation of Tetrodotoxin-Resistant Sodium Channels in Mouse Sensory Neurons by Tumor Necrosis Factor-α

“…There was no significant reduction in current amplitude in the presence of TTX. This is in agreement with previous studies showing that rat DRG neurons that express a prominent I A also express only TTX-resistant Na ϩ currents (Cardenas et al, 1999(Cardenas et al, , 2001). The peak current value at multiple potentials was recorded to generate I-V curves (Fig.…”

Direct Inhibition of Ih by Analgesic Loperamide in Rat DRG Neurons

“…The threshold for I h activation ranged between -55 and -60 mV; voltage for half-maximal activation and the slope coefficient were V 1/2 ϭ Ϫ73.2 Ϯ 0.8 mV and k ϭ 8.5 Ϯ 0.7 mV, respectively, which was similar to values reported by Cardenas et al (1999) (V 1/2 ϭ Ϫ73.3 mV, k ϭ 7.0 mV).…”

“…On the functional level, I h kinetics and pharmacology were close to those reported previously (Cardenas et al 1999;Scroggs et al 1994;Yagi and Sumino 1998). The threshold for I h activation ranged between -55 and -60 mV; voltage for half-maximal activation and the slope coefficient were V 1/2 ϭ Ϫ73.2 Ϯ 0.8 mV and k ϭ 8.5 Ϯ 0.7 mV, respectively, which was similar to values reported by Cardenas et al (1999) (V 1/2 ϭ Ϫ73.3 mV, k ϭ 7.0 mV).…”