Barttin increases surface expression and changes current properties of ClC-K channels.

@article{citeulike:604309, abstract = {The term Bartter syndrome encompasses a heterogeneous group of autosomal recessive salt-losing nephropathies that are caused by disturbed transepithelial sodium chloride reabsorption in the distal nephron. Mutations have been identified in the NKCC2 (Na(+)-K(+)-2Cl(-)) cotransporter and ROMK potassium channel, which cooperate in the process of apical sodium chloride uptake, and ClC-Kb chloride channels, which mediate basolateral chloride release. Recently, mutations in barttin, a protein not related to any known ion transporter or channel, were described in BSND, a variant of Bartter syndrome associated with sensorineural deafness. Here we show that barttin functions as an activator of ClC-K chloride channels. Expression of barttin together with ClC-K in Xenopus oocytes increased ClC-K current amplitude, changed ClC-K biophysical properties, and enhanced ClC-K abundance in the cell membrane. Co-immunoprecipitation revealed a direct interaction of barttin with ClC-K. We performed in situ hybridization on rat kidney slices and RT-PCR analysis on microdissected nephron segments to prove co-expression of barttin, ClC-K1 and ClC-K2 along the distal nephron. Functional analysis of BSND-associated point mutations revealed impaired ClC-K activation by barttin. The results demonstrate regulation of a CLC chloride channel by an accessory protein and indicate that ClC-K activation by barttin is required for adequate tubular salt reabsorption.}, address = {Department of Pediatrics, Philipps University of Marburg, Deutschhausstr. 12, 35033 Marburg, Germany. siegfried.waldegger@mailer.uni-marburg.de}, author = {Waldegger, S. and Jeck, N. and Barth, P. and Peters, M. and Vitzthum, H. and Wolf, K. and Kurtz, A. and Konrad, M. and Seyberth, H. W. }, citeulike-article-id = {604309}, doi = {http://dx.doi.org/10.1007/s00424-002-0819-8}, issn = {0031-6768}, journal = {Pflugers Arch}, keywords = {barttin, channel, chloride, expression}, month = {June}, number = {3}, pages = {411--418}, posted-at = {2006-04-27 10:36:57}, priority = {2}, title = {Barttin increases surface expression and changes current properties of ClC-K channels.}, url = {http://dx.doi.org/10.1007/s00424-002-0819-8}, volume = {444}, year = {2002} }

TY - JOUR ID - citeulike:604309 L3 - citeulike-article-id:604309 TI - Barttin increases surface expression and changes current properties of ClC-K channels. JF - Pflugers Arch VL - 444 IS - 3 SP - 411 EP - 418 AD - Department of Pediatrics, Philipps University of Marburg, Deutschhausstr. 12, 35033 Marburg, Germany. siegfried.waldegger@mailer.uni-marburg.de SN - 0031-6768 N2 - The term Bartter syndrome encompasses a heterogeneous group of autosomal recessive salt-losing nephropathies that are caused by disturbed transepithelial sodium chloride reabsorption in the distal nephron. Mutations have been identified in the NKCC2 (Na(+)-K(+)-2Cl(-)) cotransporter and ROMK potassium channel, which cooperate in the process of apical sodium chloride uptake, and ClC-Kb chloride channels, which mediate basolateral chloride release. Recently, mutations in barttin, a protein not related to any known ion transporter or channel, were described in BSND, a variant of Bartter syndrome associated with sensorineural deafness. Here we show that barttin functions as an activator of ClC-K chloride channels. Expression of barttin together with ClC-K in Xenopus oocytes increased ClC-K current amplitude, changed ClC-K biophysical properties, and enhanced ClC-K abundance in the cell membrane. Co-immunoprecipitation revealed a direct interaction of barttin with ClC-K. We performed in situ hybridization on rat kidney slices and RT-PCR analysis on microdissected nephron segments to prove co-expression of barttin, ClC-K1 and ClC-K2 along the distal nephron. Functional analysis of BSND-associated point mutations revealed impaired ClC-K activation by barttin. The results demonstrate regulation of a CLC chloride channel by an accessory protein and indicate that ClC-K activation by barttin is required for adequate tubular salt reabsorption. KW - barttin KW - channel KW - chloride KW - expression AU - Waldegger, S AU - Jeck, N AU - Barth, P AU - Peters, M AU - Vitzthum, H AU - Wolf, K AU - Kurtz, A AU - Konrad, M AU - Seyberth, HW PY - 2002/06// UR - http://dx.doi.org/10.1007/s00424-002-0819-8 ER -