The Journal of General Physiology
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Published online December 26, 2006
doi:10.1085/jgp.200609665
The Journal of General Physiology, Vol. 129, No. 1, 57-77
The Rockefeller University Press, 0022-1295 $30.00
© 2006 Coste et al.
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Pharmacological Dissection and Distribution of NaN/Nav1.9, T-type Ca2+ Currents, and Mechanically Activated Cation Currents in Different Populations of DRG Neurons



Bertrand Coste, Marcel Crest, and Patrick Delmas

Laboratoire de Neurophysiologie Cellulaire, Centre National de la Recherche Scientifique, UMR 6150, Faculté de Médecine, IFR Jean Roche, 13916 Marseille Cedex 20, France

Correspondence to Patrick Delmas: delmas.p{at}jean-roche.univ-mrs.fr

Low voltage–activated (LVA) T-type Ca2+ (ICaT) and NaN/Nav1.9 currents regulate DRG neurons by setting the threshold for the action potential. Although alterations in these channels have been implicated in a variety of pathological pain states, their roles in processing sensory information remain poorly understood. Here, we carried out a detailed characterization of LVA currents in DRG neurons by using a method for better separation of NaN/Nav1.9 and ICaT currents. NaN/Nav1.9 was inhibited by inorganic ICa blockers as follows (IC50, µM): La3+ (46) > Cd2+ (233) > Ni2+ (892) and by mibefradil, a non-dihydropyridine ICaT antagonist. Amiloride, however, a preferential Cav3.2 channel blocker, had no effects on NaN/Nav1.9 current. Using these discriminative tools, we showed that NaN/Nav1.9, Cav3.2, and amiloride- and Ni2+-resistant ICaT (AR-ICaT) contribute differentially to LVA currents in distinct sensory cell populations. NaN/Nav1.9 carried LVA currents into type-I (CI) and type-II (CII) small nociceptors and medium-A{delta}–like nociceptive cells but not in low-threshold mechanoreceptors, including putative Down-hair (D-hair) and A{alpha}/ß cells. Cav3.2 predominated in CII-nociceptors and in putative D-hair cells. AR-ICaT was restricted to CII-nociceptors, putative D-hair cells, and A{alpha}/ß-like cells. These cell types distinguished by their current-signature displayed different types of mechanosensitive channels. CI- and CII-nociceptors displayed amiloride-sensitive high-threshold mechanical currents with slow or no adaptation, respectively. Putative D-hair and A{alpha}/ß-like cells had low-threshold mechanical currents, which were distinguished by their adapting kinetics and sensitivity to amiloride. Thus, subspecialized DRG cells express specific combinations of LVA and mechanosensitive channels, which are likely to play a key role in shaping responses of DRG neurons transmitting different sensory modalities.


Abbreviations used in this paper: D-hair, Down-hair; DRG, dorsal root ganglia; HVA, high voltage–activated; ICaT, LVA T-type Ca2+ currents; LVA, low voltage–activated; TTX, tetrodotoxin.


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