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  • ENaC
  • The generalized transport reaction for Na+ channels is: Na+ (out) → Na+ (in) That for the degenerins is: Cation (out) → cation (in) ENaC consists of three different subunits: α, β, γ. (wikipedia.org)
  • The stoichiometry of these subunits is still to be verified, but ENaC is very likely to be a heterotrimeric protein like the recently analyzed acid-sensing ion channel 1 (ASIC1), which belongs to the same family. (wikipedia.org)
  • Crystal structure of ASIC1 and site-directed mutagenesis studies suggest that ENaC has a central ion channel located along the central symmetry axis in between the three subunits. (wikipedia.org)
  • selectivity filter
  • Mutation of the putative domain III selectivity filter residue of the adult rat skeletal muscle Na + channel (μ1) K1237E increased resting lidocaine block, but no change was observed in block by neutral analogs of lidocaine. (pnas.org)
  • The results demonstrate that the Na + channel selectivity filter is involved in interactions with the hydrophilic part of the drugs, and it normally limits extracellular access to and escape from their binding site just within the selectivity filter. (pnas.org)
  • Biophysical evidence suggests that the local anesthetic binding site is on the cytoplasmic side of the channel pore, lying between the selectivity filter and the channel gates ( 8 ). (pnas.org)
  • 9 ) demonstrated that quaternary ammonium molecules containing aliphatic chains bind and block Shaker K + channels by interacting with two parts of the K + channel inner pore, the P loop near the channel's selectivity filter and the S6 segment. (pnas.org)
  • They also suggested that these aromatic residues might be spatially close to the Na + channel selectivity filter, which may compose part of the binding site ( 11 ). (pnas.org)
  • Another association between local anesthetics and the selectivity filter is the finding that the membrane-impermeant local anesthetic QX314 can block the cardiac Na + channel from the outside ( 12 ) and that this is probably due to access to the internal binding site through the pore ( 13 ). (pnas.org)
  • These possible relationships between local anesthetics and the selectivity filter prompted us to investigate the roles of the selectivity filter in binding and access of the drugs by using mutagenesis of the adult rat skeletal muscle Na + channel (μ1). (pnas.org)
  • A search of the genome of a single-celled choanoflagellate (the sister group of animals) identified a gene that is homologous to animal sodium channels and has a putative ion selectivity filter intermediate between calcium and sodium channels. (pnas.org)
  • From this phylogeny we infer ancestral states of the ion selectivity filter and show that this state has been retained in the choanoflagellate and placozoan channels. (pnas.org)
  • inhibitory
  • Half-maximal inhibitory concentration (IC 50 ) was 23.3 nM and IC 80 was 122 nM ( Fig. 1 B ), considerably less than the equivalent inhibitory concentrations on BK channels ( 13 ). (pnas.org)
  • Bactridine 1-2 also fall under the sodium channel inhibitory- and β subfamily. (wikipedia.org)
  • pore
  • Neo-saxitoxin and tetrodotoxin, which occlude the channel pore, reduced the amount of QX314 bound in D400A and A1529D, respectively. (pnas.org)
  • The Shaker K + channel is thought to have a pore structure analogous to that of the Na + channel. (pnas.org)
  • Ca v and Na v channels have four domains, each of which has a pore loop ( Fig. 1 ). (pnas.org)
  • Ca v channels have acidic residues (E and D) in the pore of domains I-IV (usually E/E/E/E or E/E/D/D). Selectivity for sodium, on the other hand, is based on the residues D/E/K/A in the pore. (pnas.org)
  • Sodium channels also have a cytoplasmic loop between their third and fourth domains that swings up and occludes the channel pore just milliseconds after activation ( Fig. 1 ). (pnas.org)
  • Because of the differences in the amino acids responsible for ion selectivity, and because proteins are likely to be under strong evolutionary constraints along every point of their evolution ( 20 ), it has been suggested that channels with intermediate pore sequences may exist in extant taxa ( 3 , 21 ), and some invertebrate channels have been proposed as representatives of these intermediate states ( 21 , 22 ). (pnas.org)
  • persistent
  • suggested that inactivating and persistent sodium conductances in Purkinje cells result from expression of Rat1 and Rat6, respectively. (jneurosci.org)
  • toxin
  • Of ten resistant clones analyzed, seven lacked functional sodium channels and one had a specific 40-fold increase Kd for scorpion toxin and altered voltage dependence of scorpion toxin binding. (pnas.org)
  • extracellular
  • Lamotrigine is known to block sodium channels but it is not known whether it is extracellular or intracellular. (wikipedia.org)
  • Before an action potential occurs, the axonal membrane is at its normal resting potential, and Na+ channels are in their deactivated state, blocked on the extracellular side by their activation gates. (wikipedia.org)