Voltage-dependent Na<sup>+</sup> channels consist of the principal α-subunit (∼260 kDa), without or with auxiliary β-subunit (∼38 kDa). Nine α-subunit isoforms (Na<sub>v</sub>1.1-Na <sub>v</sub>1.9) are encoded in nine different genes (SCN1A-SCN5A and SCN8A-SCN11A). Besides initiating and propagating action potentials in established neuronal circuit, Na<sup>+</sup> channels engrave, maintain and repair neuronal network in the brain throughout the life. Adrenal chromaffin cells express Na<sub>v</sub>1.7 encoded in SCN9A, which is widely distributed among peripheral autonomic and sensory ganglia, neuroendocrine cells, as well as prostate cancer cell lines. In chromaffin cells, Na<sub>v</sub>1.7-specific biophysical properties have been characterized; physiological stimulation by acetylcholine produces muscarinic receptor-mediated hyperpolarization followed by nicotinic receptor-mediated depolarization. In human patients with Na <sub>v</sub>1.7 channelopathies, gain-of-pathological function mutants (i.e. erythermalgia and paroxysmal extreme pain disorder) or loss-of-physiological function mutant (channelopathy-associated insensivity to pain) proved the causal involvement of mutant Na<sub>v</sub>1.7 in generating intolerable pain syndrome, Na<sub>v</sub>1.7 being the first molecular target convincingly identified for pain treatment. Importantly, aberrant upregulation/hyperactivity of even the native Na<sub>v</sub>1.7 produces pain associated with inflammation, nerve injury and diabetic neuropathy in rodents. Various extra- and intracellular signals, as well as therapeutic drugs modulate the activity of Na<sub>v</sub>1.7, and also cause up- and downregulation of Na<sub>v</sub>1.7. Na<sub>v</sub>1.7 seems to play an increasing number of crucial roles in health, disease and therapeutics. © 2008 The Authors.

Wada, A., Wanke, E., Gullo, F., & Schiavon, E. (2007). Voltage-dependent Nav1.7 Sodium Channels: Multiple Roles in Adrenal Chromaffin Cells and Peripheral Nervous System. ACTA PHYSIOLOGICA, 192(2), 221-231 [10.1111/j.1748-1716.2007.01810.x].

Voltage-dependent Nav1.7 sodium channels: Multiple roles in adrenal chromaffin cells and peripheral nervous system

WANKE, ENZO;
2007

Abstract

Voltage-dependent Na+ channels consist of the principal α-subunit (∼260 kDa), without or with auxiliary β-subunit (∼38 kDa). Nine α-subunit isoforms (Nav1.1-Na v1.9) are encoded in nine different genes (SCN1A-SCN5A and SCN8A-SCN11A). Besides initiating and propagating action potentials in established neuronal circuit, Na+ channels engrave, maintain and repair neuronal network in the brain throughout the life. Adrenal chromaffin cells express Nav1.7 encoded in SCN9A, which is widely distributed among peripheral autonomic and sensory ganglia, neuroendocrine cells, as well as prostate cancer cell lines. In chromaffin cells, Nav1.7-specific biophysical properties have been characterized; physiological stimulation by acetylcholine produces muscarinic receptor-mediated hyperpolarization followed by nicotinic receptor-mediated depolarization. In human patients with Na v1.7 channelopathies, gain-of-pathological function mutants (i.e. erythermalgia and paroxysmal extreme pain disorder) or loss-of-physiological function mutant (channelopathy-associated insensivity to pain) proved the causal involvement of mutant Nav1.7 in generating intolerable pain syndrome, Nav1.7 being the first molecular target convincingly identified for pain treatment. Importantly, aberrant upregulation/hyperactivity of even the native Nav1.7 produces pain associated with inflammation, nerve injury and diabetic neuropathy in rodents. Various extra- and intracellular signals, as well as therapeutic drugs modulate the activity of Nav1.7, and also cause up- and downregulation of Nav1.7. Nav1.7 seems to play an increasing number of crucial roles in health, disease and therapeutics. © 2008 The Authors.
Si
Articolo in rivista - Articolo scientifico
Scientifica
sodium channels, chromaffin cells, peripheral nersous system
English
Wada, A., Wanke, E., Gullo, F., & Schiavon, E. (2007). Voltage-dependent Nav1.7 Sodium Channels: Multiple Roles in Adrenal Chromaffin Cells and Peripheral Nervous System. ACTA PHYSIOLOGICA, 192(2), 221-231 [10.1111/j.1748-1716.2007.01810.x].
Wada, A; Wanke, E; Gullo, F; Schiavon, E
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/8058
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