The functional expression of cloned Drosophila melanogaster and house fly (Musca domestica) voltage-sensitive sodium channels in Xenopus oocytes is enhanced, and the inactivation kinetics of the expressed channels are accelerated, by coexpression with the tipE protein, a putative sodium channel auxiliary subunit encoded by the tipE gene of D. melanogaster. These results predict the existence of...

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with infantile/childhood onset epilepsies (≥3 months of age) occur almost as often as those with an early inf...

Voltage-gated sodium channels are vital membrane proteins essential for electrical signalling; in humans, they are key targets for the development of pharmaceutical drugs. Here we report the crystal structure of an open-channel conformation of NavMs, the bacterial channel pore from the marine bacterium Magnetococcus sp. (strain MC-1). It differs from the recently published crystal structure of ...

Significance AMPA-type glutamate receptors (AMPARs) make the final step in a relay of excitability from one brain cell to another. The receptor contains an integral ion channel, which, when opened by neurotransmitter, permits sodium and other cations cross membrane. We investigated permeation sodium, potassium, cesium at atomistic level using computational molecular dynamics approach obtained t...

BACKGROUND Voltage-gated sodium channel Nav1.7 is preferentially expressed in dorsal root ganglion (DRG) and sympathetic neurons within the peripheral nervous system. Homozygous or compound heterozygous loss-of-function mutations in SCN9A, the gene which encodes Nav1.7, cause congenital insensitivity to pain (CIP) accompanied by anosmia. Global knock-out of Nav1.7 in mice is neonatal lethal rep...

Chronic and neuropathic pain constitute significant health problems affecting millions of individuals each year. Pain sensations typically originate in sensory neurons of the peripheral nervous system which relay information to the central nervous system (CNS). Pathological pain sensations can arise as result of changes in excitability of these peripheral sensory neurons. Voltage-gated sodium c...

Sepsis-associated acute renal failure is characterized by decreased GFR and tubular dysfunction. The pathogenesis of endotoxemic tubular dysfunction with failure in urine concentration and increased fractional sodium excretion is poorly understood. This study investigated the regulation of renal sodium transporters during severe inflammation in vivo and in vitro. Injection of high-dosage LPS re...

The kdr insecticide resistance trait in the house fly, Musca domestica, confers resistance to the rapid paralysis (knockdown) and lethal effects of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and pyrethroids. Flies with the kdr trait exhibit reduced neuronal sensitivity to these compounds, which are known to act at voltage-sensitive sodium channels of nerve membranes. To test the hypoth...

Arterial baroreflex sensitivity is attenuated in chronic heart failure (CHF) state, which is associated with cardiac arrhythmias and sudden cardiac death in patients with CHF. Our previous study showed that CHF-induced sodium channel dysfunction in the baroreceptor neurons was involved in the blunted baroreflex sensitivity in CHF rats. Mitochondria-derived superoxide overproduction decreased ex...