Disease relevance of Scn4a

• Hyperpolarized shifts in the voltage dependence of fast inactivation of Nav1.4 and Nav1.5 in a rat model of critical illness myopathy [1].

Psychiatry related information on Scn4a

• Mu 1 opioid receptor involvement in maternal behavior [2].

High impact information on Scn4a

• We describe the isolation and characterization of a cDNA encoding the alpha subunit of a new voltage-sensitive sodium channel, microI, from rat skeletal muscle [3].
• Sodium channels expressed in Xenopus oocytes from synthetic RNA encoding microI are blocked by tetrodotoxin and mu-conotoxin at concentrations near 5 nM [3].
• 4. Taken together, our data suggest that changes in resting potential toward more positive potentials favor states of Nav1.4 with depolarized voltage dependence of gating and thus shift voltage dependence of the sodium current [4].
• We found that microI transcripts were not expressed in brain or heart, or in the myogenic cell line L6, even after differentiation to myotubes [5].
• The blockage of skeletal muscle sodium channels by tetrodotoxin (TTX) and saxitoxin (STX) have been studied in CHO cells permanently expressing rat Nav1.4 channels [6].

Biological context of Scn4a

• We have recently described the cloning and functional expression of a new sodium channel subtype, microI, isolated from a denervated rat skeletal muscle cDNA library [5].
• TTX-sensitive currents obtained by expression in Xenopus oocytes of the alpha-subunits of the rat brain (BrnIIa) and adult skeletal muscle (microI) Na channels show abnormally slow decay kinetics [7].
• Mu1: a very high affinity subtype of enkephalin binding sites in rat brain [8].

Anatomical context of Scn4a

• NeoSTX had a higher affinity for the adult rat skeletal muscle Na+ channel (muI or Scn4a) than for STX (DeltaG approximately = 1.3 kcal/mol) [9].
• Mu-1 opioid receptors were found to be localized on the postsynaptic membrane of dendrites, extra-synaptic plasma membrane, and the surface of the small, clear vesicles in axon terminals [10].

Associations of Scn4a with chemical compounds

• Meptazinol: a novel Mu-1 selective opioid analgesic [11].
• We demonstrate here that mutation of glutamate 403 (E403) of the adult skeletal muscle microI channel (corresponding to E387 of RII) also prevents current blockade by TTX and STX, and by neo-saxitoxin [12].
• State-dependent block of rat Nav1.4 sodium channels expressed in xenopus oocytes by pyrazoline-type insecticides [13].

Analytical, diagnostic and therapeutic context of Scn4a

• Northern blot analysis indicates that the 8.5 kb microI transcript is preferentially expressed in skeletal muscle [3].
• Surprisingly, denervation of adult muscle was also followed by a rise in microI mRNA, at a time when TTX-insensitive currents reappear [5].

References