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.
Citazione: | 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. |
Tipo: | Articolo in rivista - Articolo scientifico |
Carattere della pubblicazione: | Scientifica |
Presenza di un coautore afferente ad Istituzioni straniere: | Si |
Titolo: | Voltage-dependent Nav1.7 Sodium Channels: Multiple Roles in Adrenal Chromaffin Cells and Peripheral Nervous System |
Autori: | Wada, A; Wanke, E; Gullo, F; Schiavon, E |
Autori: | |
Data di pubblicazione: | 2007 |
Lingua: | English |
Rivista: | ACTA PHYSIOLOGICA |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1111/j.1748-1716.2007.01810.x |
Appare nelle tipologie: | 01 - Articolo su rivista |