Voltage-dependent Nav1.7 Sodium Channels: Multiple Roles in Adrenal Chromaffin Cells and Peripheral Nervous System

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