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In our laboratory we examine the structure, function and regulation of two types of sodium channels: the Epithelial Na + Channel (ENaC) and Acid Sensing Ion Channels (ASIC). These proteins are structurally related but serve very different functions. ENaC is expressed in the apical side of epithelial cells involved in sodium absorption such as in kidney, lung and colon. Mutations in the human ENaC genes produce disorders of whole-body sodium balance and are characterized by hypertension or sodium wasting. Our current work centers on mechanisms that regulate activity, expression and traffic of ENaC in epithelial cells specifically, on the role of a kinase known as serum-and glucocorticoid-induced kinase or Sgk1.
The ASICs are expressed in neurons of the central and peripheral nervous systems. External protons gate ASIC but other stimuli are likely to be more important physiological agonists. These channels have been implicated in many functions including nociception, mechanoperception and modulation of synaptic transmission. Our work centers in the elucidation of the biophysical properties and gating of ASICs from many vertebrate species.
We use a broad range of experimental approaches and techniques that include electrophysiology (patch-clamp, two-electrode voltage clamp, short-circuit current), cloning of channels from evolutionary distant species, modifications of channels and their expression in oocytes, cell lines and in mice either trangenics or knockins.
Recent publications:
Arteaga MF, Wang L, Ravid T, Hochstrasser M and Canessa CM (2006) A short amphipathic helix targets Sgk1 to the ER-associated ubiquitin-conjugation machinery. PNAS USA 103, 11178-83
Zhang P, Sigworth FJ and Canessa CM (2006) Gating of Acid-sensitive Ion Channel-1: Release of Ca 2+ Block vs. Allosteric Mechanism. J Gen Physiol 127, 109-17
Alvarez de la Rosa D, Gimenez I, Forbush B and Canessa CM (2006) SGK1 activates Na+-K+-ATPase in amphibian renal epithelial cells. Am J Physiol Cell Physiol 290, C492-8
Coric T, Zheng D, Gerstein M, Canessa CM (2005) Proton sensitivity of ASIC1 appeared with the rise of fishes by changes of residues in the region that follows TM1 in the ectodomain of the channel. J Physiol 568, 725-35.
Arteaga MF and Canessa CM (2005) Functional specificity of Sgk1 and Akt1 on ENaC activity. Am J PhysiolRenal Physiol 289, F90-96
Alvarez de la Rosa D, Paunescu TG, Els JE, Helman SI and Canessa CM (2004) Mechanism of regulation of epithelial sodium channel by SGK1 in A6 cells. J Gen Physiol 124, 395-407
Coric T, Hernandez N, Alvarez De La Rosa D, Shao D, Wang T and Canessa CM (2003) Expression of ENaC and serum and glucocorticoid induced kinase 1 in the rat intestinal epithelium. Am J Physiol Gastrointest Liver Physiol. 286, G663-G670
Coric T, Zhang P, Todorovic N and Canessa CM (2003) The extracellular domain determines the kinetics of desensitization in ASIC1. J Biol Chem 278, 45240-4524.
Alvarez de la Rosa D, Todorovic N, Shao D, Wang T and Canessa CM (2003) Cellular distribution, levels of expression and subcellular localization of the serum- and glucocorticoid-induced kinase in the rat kidney. J Physiol 551, 455-466
Alvarez de la Rosa D and Canessa CM (2003) The role of the serum- and glucocorticoid-kinase in hormonal regulation of the epithelial sodium channel in A6 cells. A J Physiol Cell Physiol. 254, C404-C414
Alvarez de la Rosa D, Krueger S, Kolar A, Fitzsimonds RM and Canessa CM (2003) Localization and function of ASIC1 in the central nervous system. J Physiol 546, 77-87.
cecilia.canessa@yale.edu 
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