A single serine residue confers tetrodotoxin insensitivity on the rat sensory-neuron-specific sodium channel SNS

AbstractSensory neurons express a sodium channel (SNS) that is highly resistant to block by tetrodotoxin (IC50=60 μM). SNS is 65% homologous to the cardiac sodium channel, in which a single hydrophilic residue in the SS2 segment is critical for tetrodotoxin resistance. By site-directed mutagenesis, we have substituted phenylalanine for serine at the equivalent position in SNS: this mutated (S356F) SNS channel is functionally similar to wild-type SNS when expressed in Xenopus oocytes, but is potently blocked by tetrodotoxin and saxitoxin with IC50s of 2.8 nM and 8.2 nM, respectively. These data provide clues to the rational design of selective blockers of SNS with potential as analgesic drugs

Nonlinear dynamics of soft boson collective excitations in hot QCD plasma III: bremsstrahlung and energy losses

Within of the framework of semiclassical approximation a general formalism for deriving an effective current generating bremsstrahlung of arbitrary number of soft gluons (longitudinal or transverse ones) in scattering of higher-energy parton off thermal parton in hot quark-gluon plasma with subsequent extension to two and more scatterers, is obtained. For the case of static color centers an expression for energy loss induced by usual bremsstrahlung of lowest-order with allowance for an effective temperature-induced gluon mass and finite mass of the projectile (heavy quark), is derived. The detailed analysis of contribution to radiation energy loss associated with existence of effective three-gluon vertex induced by hot QCD medium, is performed. It is shown that in general, the bremsstrahlung associated with this vertex have no sharp direction (as in the case of usual bremsstrahlung) and therefore here, we can expect an absence of suppression effect due to multiple scattering. For the case of two color static scattering centers it was shown that the problem of calculation of bremsstrahlung induced by four-gluon hard thermal loop (HTL) vertex correction can be reduced to the problem of the calculation of bremsstrahlung induced by three-gluon HTL correction. It was shown that for limiting value of soft gluon occupation number $N_{\bf k}\sim 1/\alpha_s$ all higher processes of bremsstrahlung of arbitrary number of soft gluons become of the same order in coupling, and the problem of resummation of all relevant contributions to radiation energy loss of fast parton, arises. An explicit expression for matrix element of two soft gluon bremsstrahlung in small angles approximation is obtained.Comment: 68 pages, 9 EPS figures; added new sections 8, 10 and reference

Knockdown of zebrafish Nav1.6 sodium channel impairs embryonic locomotor activities

[[abstract]]Although multiple subtypes of sodium channels are expressed in most neurons, the specific contributions of the individual sodium channels remain to be studied. The role of zebrafish Nav1.6 sodium channels in the embryonic locomotor movements has been investigated by the antisense morpholino (MO) knockdown. MO1 and MO2 are targeted at the regions surrounding the translation start site of zebrafish Nav1.6 mRNA. MO3 is targeted at the RNA splicing donor site of exon 2. The correctly spliced Nav1.6 mRNA of MO3 morphants is 6% relative to that of the wild-type embryos. Nav1.6-targeted MO1, MO2 and MO3 attenuate the spontaneous contraction, tactile sensitivity, and swimming in comparison with a scrambled morpholino and mutated MO3 morpholino. No significant defect is observed in the development of slow muscles, the axonal projection of primary motoneurons, and neuromuscular junctions. The movement impairments caused by MO1, MO2, and MO3 suggest that the function of Nav1.6 sodium channels is essential on the normal early embryonic locomotor activities.[[notice]]補正完畢[[journaltype]]國