Human cardiac sodium channel

Yang P, Kupershmidt S, Roden DM. Cloning and initial characterization of the human cardiac sodium channel (SCN5A) promoter. Cardiovasc Res 2004 61 56-65. 

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. 

Ion channel modulation represents another approach to positive inotropy [13]. Sodium channel modulators increase Na+ influx and prolong the plateau phase of the action potential sodium/calcium exchange then leads to an increase in the level of calcium available to the contractile elements, thus increasing the force of cardiac contraction [13,14]. Synthetic compounds such as DPI 201-106 and BDF 9148 (Figure 1) increase the mean open time of the sodium channel by inhibiting channel inactivation [15]. Importantly, BDF 9148 remains an effective positive inotropic compound even in severely failing human myocardium [16] and in rat models of cardiovascular disease [17]. Modulators of calcium and potassium channel activities also function as positive inotropes [13], but in the remainder of this article we shall focus on sodium channel modulators. 

Studies on human embryotic cells demonstrated that ciguatoxins target and bind to site 5 voltage gated sodium channels in both cardiac and muscle cells. 

Nuss HB, Chiamvimonvat N, Perez-Garcia MT, Tomaselli GF, Marban E 1995 Functional association of the beta 1 subunit with human cardiac (hHl) and rat skeletal muscle (/tl) sodium channel alpha subunits expressed in Xenopus oocytes. J Gen Physiol 106 1171—1191... 

Trenor B, Gomis-Tena J, Cardona K et al (2013) In silico assessment of drug safety in human heart applied to late sodium current blockers. Channels (Austin) 7 249-262 Valerio LG Jr, Balakrishnan S, Fiszman ML et al (2013) Development of cardiac safety translational tools for QT prolongation and torsade de pointes. Expert Opin Drug Metab Toxicol 9 801-815... 

---