Inactivation Na+ channel

The molecular mechanism of local anesthesia, the location of the local anesthetic dibucaine in model membranes, and the interaction of dibucaine with a Na+-channel inactivation gate peptide have been studied in detail by 2H- and 1H-NMR spectroscopy [24]. Model membranes consisted of PC, PS, and PE. Dibucaine was deuterated at H9 and H3 of the butoxy group and at the 3-position of the quinoline ring. 2H-NMR spectra of the multilamellar dispersions of the lipid mixtures were obtained. In addition, spectra of deuterated palmitic acids incorporated into mixtures containing cholesterol were obtained and the order parameter, SCD, for each carbon... 

Fig. 5.5 A hinged-lid model for Na+-channel inactivation and schematic representation of the interaction between a local anesthetic drug and the amino acid residues in the inactivation gate. (Reprinted from Fig. 2 of ref.

Na+ Channel inactivation leading to Elevated action potential threshold Decreased nerve conduction and velocity Decreased Na+ leak and decreased likelihood of Na+ gradient collapse Stabilized Na+ gradient-linked transporters (glucose, creatine, Ca2+, H+, transmitters)... 

Gonoi T, Hille 1987 Gating of Na channels. Inactivation modifiers discriminate among models. J Gen Physiol 89 253-274... 

Kellenberger S, Scheuer T, CatteraU WA 1996 Movement of the Na channel inactivation gate during inactivation. J Biol Chem 271 30971-30979... 

West JW, Patton DE, Scheuer T, Wang Y, Goldin AL, Catterall WA 1992 A cluster of hydrophobic amino acid residues required for fast Na channel inactivation. Proc Natl Acad Sci USA 89 10910-10914... 

Indeed, an A-terminal peptide alone can restore inactivation to a channel rendered noninactivating by mutation (Fig. 28.17). ° A similar tethered antagonist exists for the voltage-gated Na channel where the cytoplasmic loop linking domains III and IV is critical to the inactivation process. A peptide derived from this sequence is capable of producing Na channel inactivation. ... 

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