TABLE 6

Distribution of Nav subtypes and efficacy of inhibitors

IsoformDistributionPotential Effects/Side EffectsSelective Toxin InhibitorsReferences
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 conotoxinsCatterall 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-ConotoxinsCatterall 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 conotoxinsFelts et al., 1997; Hains et al., 2003; Catterall et al., 2005a; Catterall, 2010
Nav1.4 (SCN4A)Skeletal muscleMuscle dysfunctionμ-ConotoxinsCatterall et al., 2005a; Schroeder et al., 2008; Catterall, 2010; Wilson et al., 2011a
Nav1.5 (SCN5A)Cardiac muscle, embryonic DRGCardiac side effectsNo selective conotoxinsCatterall 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 conotoxinsCatterall 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, MrVIBEkberg 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 knownCatterall et al., 2005a; Cummins and Rush, 2007; O'Brien et al., 2008
  • PNS, peripheral nervous system.