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Physiology. structure and function of potassium channels. role of potassium channels in causing diseaseIon-channels are membrane proteins that control a large number of biological functions. They modulate the activity of excitable cells and shape signaling events in non-excitable cells such as hormone and transmitter release. The research of the laboratory is focused on understanding the properties and the role of potassium channels expressed in human heart and in the nervous system of the nematode C. elegans. IKr is an important repolarizing potassium current in human ventricle. The crucial role of this current is corroborated in a subset of patients with congenital and acquired prolongation of the QT interval that predisposes to a specific form of polymorphic ventricular tachycardia known as Long QT syndrome (LQTs). A common cause of acquired LQTs is a side effect of common medications of diverse therapeutic and structural classes. Most of these medications block IKr leading to delayed repolarization. Ongoing research employs a multidisciplinary approach (genetics. electrophysiology. molecular biology. biochemistry) to investigate the molecular bases for IKr susceptibility to unspecific medications in patients with drug-induced arrhythmia. Deciphering mechanisms of nervous system function is a major focus of current neuroscience research. Invertebrate model systems are making a significant contribution to this effort since many details of basic neuronal function are remarkably conserved. The comparative simplicity of C. elegans invites a comprehensive description of the development. structure and function of the entire nervous system. Recently. we have cloned and expressed functionally a voltage-gated potassium channel. KVS. expressed in C. elegans nervous system. The recent discovery of this channel put us in a unique position to study mechanisms of sensory perception. information integration and cognition. Selected PublicationsCai SQ, Li W, Sesti F. (2007) Multiple modes of a-type potassium current regulation. Curr Pharm Des. 13(31):3178-84. Hernandez L, Park KH, Cai SQ, Qin L, Partridge N, Sesti F. (2007) The antiproliferative role of ERG K+ channels in rat osteoblastic cells. Cell Biochem Biophys. 47(2):199-208. Wang Y, Sesti F. (2007) Molecular mechanisms underlying KVS-1-MPS-1 complex assembly. Biophys J. 93(9):3083-91. Park KH, Sesti F. (2007) An arrhythmia susceptibility gene in Caenorhabditis elegans. J Biol Chem. 282(27):19799-807. Cai SQ, Sesti F. (2007) A new mode of regulation of N-type inactivation in a Caenorhabditis elegans voltage-gated potassium channel. J Biol Chem. 282(25):18597-601. Cai SQ, Park KH, Sesti F. (2006) An evolutionarily conserved family of accessory subunits of K+ channels. Cell Biochem Biophys 46(1):91-9. Review. Cai. S-Q. Hernandez. L. Wang. Y. Park. KH. Sesti. F. (2005) MPS-1 is a K+ channel b-subunit and a serine/threonine kinase. Nat Neurosci. 8(11):1503-9. Park. KH. Cai. SQ. Hernandez. L. Wang. Y. Sesti. F. (2005) A family of K+ channel ancillary subunits regulate taste sensitivity in C. elegans. JBC 280(23):21893-9. Wang. Y. Park. KH. Hernandez. Cai. LQ. Sesti. F. (2004) Biophysical and biomedical aspects of KCNE potassium channel ancillary subunits" Book chapter Review. Recent Res. Dev. Biophys. 3:1-12.ISBN: 81-7895-130-4 Park. KH. Chhowalla. M. Iqbal. Z and Sesti. F. Single-walled carbon nanotubes: A new class of ion-channel blockers. JBC published September 30. 2003 as doi:10.1074/jbc.M310216200. Park. KH. Kwok. SM. Sharon. C. Baerga. R. Sesti. F. (2003). N-glycosylation-dependent block is a novel mechanism for drug-induced cardiac arrhythmia. The Faseb j express article 10.1096/fj.03-0577fje. Bianchi. L. Kwok. SM. Driscoll. M and Sesti. F. (2003) A potassium channel-MiRP complex controls chemosensation in C. elegans. JBC 278(14): 12415-24. Sesti. F. Rajan. S. Gonzalez-Colaso. R. Nikolaeva. N and Goldstein. SAN. (2003). Hyperpolarization moves S4 sensors inward to open MVP. a methanococcal voltage-gated potassium channel Nat. Neurosci. 6(4): 353-361. |
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