Sodium channels mutations

In the Long QT Syndrome (LQTS), the repolarization phase of the cardiac muscle is delayed, rendering the heart vulnerable to an arrhythmia known as torsade de pointes. LQTS is associated with five genes encoding ion channels. LQTS type 3 (LQT3) results from mutations of Nav1.5, which cause persistent sodium cunent. In contrast, sodium channel mutations associated with Biugada syndrome reduce the expression level of cardiac sodium channels. 

Meisler MH, Kearney JA (2005) Sodium channel mutations in epilepsy and other neurological disorders. J Clin Invest 115 2010-2017. 

Bricelj VM, Connell L, Konoki K, MacQuarrie SP, Scheuer T, Catterall WA, Trainer VL (2005) Sodium channel mutation leading to saxitoxin resistance in clams increases risk of PSP. Nature 434 763-767... 

Wang, Q., Shen, J.X., Li, Z.Z., Timothy, K Vincent, G.M., Priori, S.G., Schwartz, P.J. and Keating, M.T. (1995) Cardiac sodium-channel mutations in patients with long Qt syndrome. An inherited cardiac-arrhythmia. Human Molecular Genetics, 4, 1603—1607. 

Jurkat-Rott K, Mitrovic N, Hang C, Kouzmekine A, Iaizzo P, Herzog J, Lerche H, Nicole S, Vale-Santos J, Chauveau D, Fontaine B, Lehmann-Horn F (2000b) Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. Proc Natl Acad Sci U S A 97 9549-9554. 

Epilepsy affects 0.5% of the world s population and can have a multitude of underlying etiologies, including several mutations in CNS sodium channels. Sodium channel mutations linked to human epileptic syndromes typically shift activation to more hyperpolarized potentials, slow inactivation kinetics, accelerate recovery from inactivation, and/or increase the persistent current [48]. Seemingly paradoxically, some mutations appear to result in non-functional channels [48-50]. 

Chahine M, George AL Jr, Zhou M, Ji S, Sun W, Barchi RL, Horn R. Sodium channel mutations in paramyotonia congenita uncouple inactivation from activation. Neuron 1994 12 281-294. 

H. A sodium channel mutation causing epilepsy in man exhibits subtle defects in fast inactivation and activation in vitro. J. Physiol. 

Tan HL, Bink-Boelkens MT, Bezzina CR, Viswanathan PC, Beaufort-Krol GC, et al. 2001. A sodium-channel mutation causes isolated cardiac conduction disease. Nature 409 1043 17... 

Spampanato J, Escayg A, Meisler MH, Goldin AL 2001 Functional effects of two voltage-gated sodium channel mutations that cause generalized epilepsy with febrile seizures plus type 2. J Neurosci 21 7481-7490... 

Cannon SC, Strittmatter SM 1993 Functional expression of sodium channel mutations identified in families with periodic paralysis. Neuron 10 317—326... 

Yang N, Ji S, Zhou M et al 1994 Sodium channel mutations in paramyotonia congenita exhibit similar biophysical phenotypes in vitro. Proc Natl Acad Sci USA 91 12785-12789... 

Ptacek LJ, Tawil R, Griggs RC et al 1994a Sodium channel mutations in acetazolamide-responsive myotonia congenita, paramyotonia congenita, and hyperkalemic periodic paralysis. Neurology 44 1500-1503... 

Chen J, Makiyama T, Wuriyanghai Y et al (2016) Cardiac sodium channel mutation associated with epinephrine-induced QT prolongation and sinus node dysfunction. Heart Rhythm 13 289-298... 

A 45-year-old man with no history of cardiac disease had a seizure. His electrocardiogram was normal He then suddenly developed a monomorphic wide-complex ventricular tachycardia for which he was given lidocaine 70 mg followed by a continuous infusion of 1 mg/minute. This led to ST segment elevation in leads Vl-3, which persisted even 1 year later. There was no evidence of myocardial infarction and he had no chest pain. He was genotyped and the sodium channel mutation was discovered. 

In this article, the level of susceptibility to various insecticides in different human head louse populations in the US was investigated to assess the distribution of resistance. We also reported on the molecular mechanisms of head louse resistance to pyrethroid mediated by sodium channel mutations. Also discussed were the genotyping techniques for resistance monitoring and the... 

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