Isoform | Distribution | Potential Effects/Side Effects | Selective Toxin Inhibitors | References |
---|---|---|---|---|
Nav1.1 (SCN1A) | Located primarily in neuronal soma. Found widely in CNS and peripheral neurons (including DRG) cardiac myocytes (T-tubules) (cortex, hippocampus, cerebellum), PNS: DRG, motor neurons. | Widespread effects on the nervous and cardiovascular systems. | No selective conotoxins | Catterall et al., 2005a; Catterall, 2010 |
Nav1.2 (SCN2A) | Located primarily in axons, node of Ranvier. Found in CNS low expression in adult DRG. | Widespread effects on the nervous and cardiovascular systems. | μ-Conotoxins | Catterall et al., 2005a; Schroeder et al., 2008; Catterall, 2010; Wilson et al., 2011a |
Nav1.3 (SCN3A) | Widely distributed in embryonic nervous system but declines postnatally; adult rat CNS, particularly dorsal spinal cord; also upregulated after injury; adult human CNS. | Limited evidence for analgesia. If restricted to periphery, side effects should be minimal; intrathecal CNS side effects possible. | No selective conotoxins | Felts et al., 1997; Hains et al., 2003; Catterall et al., 2005a; Catterall, 2010 |
Nav1.4 (SCN4A) | Skeletal muscle | Muscle dysfunction | μ-Conotoxins | Catterall et al., 2005a; Schroeder et al., 2008; Catterall, 2010; Wilson et al., 2011a |
Nav1.5 (SCN5A) | Cardiac muscle, embryonic DRG | Cardiac side effects | No selective conotoxins | Catterall et al., 2005a; Catterall, 2010 |
Nav1.6 (SCN8A) | Highly localized in nodes of Ranvier in CNS and PNS, including DRG. | Widespread effects on the nervous and cardiovascular systems. | No selective conotoxins | Catterall et al., 2005a; Catterall, 2010 |
Nav1.7 (SCN9A) | High expression in small sensory (DRG) neurons and autonomic neurons, also Schwann cells, CD1 + dendritic cells, and some endocrine cells (adrenal medulla). | Analgesic effects. Possible autonomic side effects but autonomic function seems normal with loss-of-function mutations; olfactory side effects. | No selective conotoxins (ProTx-II, huwentoxin-IV) | Catterall et al., 2005a; Cummins and Rush, 2007; Schmalhofer et al., 2008; Xiao et al., 2008a; Xiao et al., 2008b |
Nav1.8 (SCN10A) | Small- to medium-sized (presumably nociceptive) DRG neurons, also found in retina and cardiac myocytes. | Analgesic effects. Visual and cardiac side-effects likely from distributional and human mutation studies. | MrVIA, MrVIB | Ekberg et al., 2006; Cummins and Rush, 2007; O'Brien et al., 2008; Chambers et al., 2010 |
Nav1.9 (SCN11A) | Small-diameter, mostly unmyelinated DRG neurons, also found in retina. | Potential analgesic effects. Potential visual effects. | None known | Catterall et al., 2005a; Cummins and Rush, 2007; O'Brien et al., 2008 |
PNS, peripheral nervous system.