Voltage-dependent Nav1.7 sodium channels: multiple roles in adrenal chromaffin cells and peripheral nervous system
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Author Posting. © The Authors 2007 This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in "Acta physiologica", 192(2) pp221-232. http://dx.doi.org/10.1111/j.1748-1716.2007.01810.xVoltage-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–Nav1.9) 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 Nav1.7 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.
- Acta physiologica : official journal of the Federation of European Physiological Societies
Acta physiologica : official journal of the Federation of European Physiological Societies 192(2), 221-231, 2007-11-16