Single amino acids in the carboxyl terminal domain of aquaporin-1 contribute to cGMP-dependent ion channel activation 英文参考文献.docVIP

BMC Physiology BioMedCentral Research article Open Access Single amino acids in the carboxyl terminal domain of aquaporin-1 contribute to cGMP-dependent ion channel activation Daniela Boassa1 and Andrea J Yool*1,2,3 Address: 1Program in Neuroscience, University of Arizona, Tucson, Arizona, 85724-5051, USA, 2Dept. of Physiology, University of Arizona College of Medicine, Tucson, Arizona, USA and 3Dept. of Pharmacology, University of Arizona College of Medicine, Tucson, Arizona, USA Email: Daniela Boassa - dboassa@; Andrea J Yool* - ayool@ * Corresponding author Published: 15 October 2003 Received: 22 April 2003 Accepted: 15 October 2003 BMC Physiology 2003, 3:12 This article is available from: /1472-6793/3/12 ? 2003 Boassa and Yool; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the articles original URL. Abstract Background: Aquaporin-1 (AQP1) functions as an osmotic water channel and a gated cation channel. Activation of the AQP1 ion conductance by intracellular cGMP was hypothesized to involve the carboxyl (C-) terminus, based on amino acid sequence alignments with cyclic- nucleotide-gated channels and cGMP-selective phosphodiesterases. Results: Voltage clamp analyses of human AQP1 channels expressed in Xenopus oocytes demonstrated that the nitric oxide donor, sodium nitroprusside (SNP; 3–14 mM) activated the ionic conductance response in a dose-dependent manner. Block of soluble guanylate cyclase prevented the response. Enzyme immunoassays confirmed a linear dose-dependent relationship between SNP and the resulting intracellular cGMP levels (up to 1700 fmol cGMP /oocyte at 14 mM SNP). Results here are the first to show that the efficacy of ion channel activation is decreased by mutations of AQP1 at conserved residues