Pharmacological Dissection and Distribution of NaN/Nav1.9, T-type Ca2+ Currents, and Mechanically Activated Cation Currents in Different Populations of DRG Neurons

Journal of General Physiology - Tập 129 Số 1 - Trang 57-77 - 2007
Bertrand Coste1, Marcel Crest1, Patrick Delmas1
1Laboratoire de Neurophysiologie Cellulaire, Centre National de la Recherche Scientifique, UMR 6150, Faculté de Médecine, IFR Jean Roche, 13916 Marseille Cedex 20, France

Tóm tắt

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-Aδ–like nociceptive cells but not in low-threshold mechanoreceptors, including putative Down-hair (D-hair) and Aα/β 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 Aα/β-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 Aα/β-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.

Từ khóa


Tài liệu tham khảo

1989, J. Physiol., 412, 181, 10.1113/jphysiol.1989.sp017610

1996, Nature., 379, 257, 10.1038/379257a0

1973

1992, Science., 257, 248, 10.1126/science.1321496

2003, J. Physiol., 548, 373, 10.1113/jphysiol.2003.039131

2006, Cell., 124, 1269, 10.1016/j.cell.2006.02.023

2001, J. Neurosci., 21, 6077, 10.1523/JNEUROSCI.21-16-06077.2001

1994, J. Clin. Neurophysiol., 11, 534, 10.1097/00004691-199411000-00002

2002, J. Neurosci., 22, 10277, 10.1523/JNEUROSCI.22-23-10277.2002

1985, Pflugers Arch., 403, 360, 10.1007/BF00589247

2005, EMBO J., 24, 315, 10.1038/sj.emboj.7600515

1984, Nature., 310, 501, 10.1038/310501a0

1995, J. Neurophysiol., 74, 1870, 10.1152/jn.1995.74.5.1870

2001, Annu. Rev. Neurosci., 24, 487, 10.1146/annurev.neuro.24.1.487

1997, J. Hypertens. Suppl., 15, S17, 10.1097/00004872-199715055-00004

2004, Mol. Cell. Neurosci., 26, 123, 10.1016/j.mcn.2004.01.015

1998, Circ. Res., 83, 103, 10.1161/01.RES.83.1.103

1999, J. Neurosci., 19, RC43, 10.1523/JNEUROSCI.19-24-j0001.1999

2004, Cell., 118, 145, 10.1016/j.cell.2004.07.007

2000, Nat. Neurosci., 3, 670, 10.1038/76621

1998, Proc. Natl. Acad. Sci. USA., 95, 8963, 10.1073/pnas.95.15.8963

1998, J. Physiol., 513, 857, 10.1111/j.1469-7793.1998.857ba.x

2003, Pain., 105, 159, 10.1016/S0304-3959(03)00177-5

2002, J. Neurosci., 22, RC228, 10.1523/JNEUROSCI.22-12-j0001.2002

2004, J. Physiol., 556, 691, 10.1113/jphysiol.2003.058693

2004, J. Neurosci., 24, 8480, 10.1523/JNEUROSCI.1598-04.2004

2002, J. Neurosci., 22, 7425, 10.1523/JNEUROSCI.22-17-07425.2002

2005, J. Physiol., 565, 927, 10.1113/jphysiol.2005.086199

2006, J. Neurosci., 26, 7281, 10.1523/JNEUROSCI.1072-06.2006

1987, J. Physiol., 394, 173, 10.1113/jphysiol.1987.sp016865

2002, Biophys. J., 83, 229, 10.1016/S0006-3495(02)75164-3

1992, J. Neurophysiol., 68, 213, 10.1152/jn.1992.68.1.213

2001, J. Neurophysiol., 86, 1351, 10.1152/jn.2001.86.3.1351

2006, Pain., 120, 3, 10.1016/j.pain.2005.11.002

1996, Annu. Rev. Physiol., 58, 329, 10.1146/annurev.ph.58.030196.001553

2001, Neuron., 31, 35, 10.1016/S0896-6273(01)00343-9

2005, J. Comp. Neurol., 493, 596, 10.1002/cne.20794

1975, Nature., 257, 691, 10.1038/257691a0

2002, J. Gen. Physiol., 120, 159, 10.1085/jgp.20018536

2004, J. Gen. Physiol., 124, 27, 10.1085/jgp.200409054

2006, Neuron., 50, 277, 10.1016/j.neuron.2006.03.042

2002, Exp. Physiol., 87, 239, 10.1113/eph8702350

1999, J. Neurosci., 19, 1912, 10.1523/JNEUROSCI.19-06-01912.1999

2005, Pflugers Arch., 451, 454, 10.1007/s00424-005-1463-x

2004, J. Neurobiol., 61, 30, 10.1002/neu.20078

2000, J. Pharmacol. Exp. Ther., 295, 302

2004, Pflugers Arch., 449, 76, 10.1007/s00424-004-1315-0

1999, Neurosci. Lett., 273, 179, 10.1016/S0304-3940(99)00665-5

2005, Neuroscience., 131, 499, 10.1016/j.neuroscience.2004.11.030

2004, Mol. Pharmacol., 66, 1652, 10.1124/mol.66.6.1652

2005, J. Neurosci., 25, 8766, 10.1523/JNEUROSCI.2527-05.2005

1985, Nature., 316, 440, 10.1038/316440a0

2003, Physiol. Rev., 83, 117, 10.1152/physrev.00018.2002

1998, Nature., 391, 896, 10.1038/36110

2000, J. Neurophysiol., 84, 2365, 10.1152/jn.2000.84.5.2365

2002, Neuroscience., 115, 15, 10.1016/S0306-4522(02)00409-8

2000, Nature., 407, 1007, 10.1038/35039512

2005, Proc. Natl. Acad. Sci. USA., 102, 9382, 10.1073/pnas.0501549102

1998, J. Physiol., 511, 771, 10.1111/j.1469-7793.1998.771bg.x

1996, J. Biol. Chem., 271, 5953, 10.1074/jbc.271.11.5953

1992, J. Physiol., 445, 639, 10.1113/jphysiol.1992.sp018944

1992, J. Physiol., 454, 299, 10.1113/jphysiol.1992.sp019265

2003, Nat. Neurosci., 6, 724, 10.1038/nn1076

1999, J. Neurosci., 19, 1895, 10.1523/JNEUROSCI.19-06-01895.1999

1988, Science., 240, 213, 10.1126/science.2451291

1998, Nat. Neurosci., 1, 653, 10.1038/3652

1998, J. Neurophysiol., 79, 240, 10.1152/jn.1998.79.1.240

2002, Brain Res., 951, 336, 10.1016/S0006-8993(02)03350-4

1990, Pflugers Arch., 417, 213, 10.1007/BF00370702

1998, Curr. Opin. Neurobiol., 8, 418, 10.1016/S0959-4388(98)80070-6

2005, Neuron., 46, 9, 10.1016/j.neuron.2005.03.011

1999, Proc. Natl. Acad. Sci. USA., 96, 7635, 10.1073/pnas.96.14.7635

1989, Proc. Natl. Acad. Sci. USA., 86, 6802, 10.1073/pnas.86.17.6802

2004, J. Neurobiol., 61, 55, 10.1002/neu.20094

Thông tin
Thông tin xuất bản

Journal of General Physiology

Tập 129 Số 1

57-77

Thông tin tác giả