Aquaporin channel

Higher vasopressin concentrations are linked to dilutional hyponatremia and a poor prognosis in HF. Vasopressin exerts its effects through vasopressin type la (Vla) and vasopressin type 2 (V2) receptors.5,7 Vasopressin type la stimulation leads to vasoconstriction, while actions on the V2 receptor cause free water retention through aquaporin channels in the collecting duct. Vasopressin increases preload, afterload, and myocardial oxygen demand in the failing heart. 

Water molecules flow through an AQP-1 channel at the rate of about 109 s 1. For comparison, the highest known turnover number for an enzyme is that for catalase, 4 X 107 s-1, and many enzymes have turnover numbers between 1 s 1 and 104 s 1 (see Table 6-7). The low activation energy for passage of water through aquaporin channels (AG < 15 kJ/mol) suggests that water moves through the channels in a continuous... 

Chen H, Ilan B, Wu Y, Zhu F, Schuiten K, Voth GA (2007) Charge delocalization in proton channels, I the aquaporin channels and proton blockage. Biophys J 92 46-60... 

This selective transport across cellular membranes is carried out by two broad classes of specialized proteins, which are assodated with or embedded in those lipid bilayers channels and transmembrane transporters. They work by different mechanisms Whereas channels catalyze the passage of ions (or water and gas in the case of the aquaporin channel) (Agre, 2006) across the membrane through a watery pore spanning the membrane-embedded protein, transporters are working via a cycle of conformational changes that expose substrate-binding sites alternately to the two sides of the membrane (Theobald Miller, 2010). 

Li, H., Lee, S., and Jap, B., 1997. Molecular de.sign of aquaporin-1 water channel as revealed by electron cry.stallography. Nature Structural Biology 4 263-265. 

Aquaporins are central players in mammalian physiology, but are also important in microorganisms and plants. The number of AQPs in plants is quite high angiosperms species, for example, express approximately 35 different AQPs divided into four families on the basis of their sequence. Moreover, plant AQPs might be considered multifunctional channels for their different transport properties. 

Robben JH, Knoers NV, Deen PM (2006) Cell biological aspects of the vasopressin 1ype-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus. Am J Physiol Renal Physiol 291 F257-F270... 

The CaR regulates numerous biological processes, including the expression of various genes (e.g., PTH) the secretion of hormones (PTH and calcitonin), cytokines (MCP-1), and calcium (e.g., into breast milk) the activities of channels (potassium channels) and transporters (aquaporin-2) cellular shape, motility (of macrophages), and migration cellular adhesion (of hematopoietic stem cells) and cellular proliferation (of colonocytes), differentiation (of keratinocytes), and apoptosis (of H-500 ley dig cancer cells) [3]. 

Aquaporins Are Proteins That Form Water Channels in Certain Membranes... 

Water reabsorption. Water is reabsorbed passively by way of osmosis from many regions of the tubule. As with sodium and chloride, 65% of the filtered water is reabsorbed from the proximal tubule. An additional 15% of the filtered water is reabsorbed from the descending limb of the Loop of Henle. This reabsorption occurs regardless of the water content of the body. The water enters the tubular epithelial cells through water channels, also referred to as aquaporins. These channels are always open in the early regions of the tubule. 

The QM/MM and ab initio methodologies have just begun to be applied to challenging problems involving ion channels [73] and proton motion through them [74]. Reference [73] utilizes Hartree-Fock and DFT calculations on the KcsA channel to illustrate that classical force fields can fail to include polarization effects properly due to the interaction of ions with the protein, and protein residues with each other. Reference [74] employs a QM/MM technique developed in conjunction with Car-Parrinello ab initio simulations [75] to model proton and hydroxide ion motion in aquaporins. Due to the large system size, the time scale for these simulations was relatively short (lOps), but the influences of key residues and macrodipoles on the short time motions of the ions could be examined. 

Wang, Y. Schulten, K. Tajkhorshid, E., What makes an aquaporin a glycerol channel A comparative study of AqpZ and GlpF, Structure 2005,13, 1107-1118. 

Agre, P. (2004) Aquaporin water channels. Angewandte Chemie-Intemational Edition, 43, 4278-4290. 

Saadoun, S., Papadopoulos, M. C., Davies, D. C., Bell, B. A. and Krishna, S. Increased aquaporin 1 water channel expression in human brain tumours. Br. J. Cancer 87 621-3,... 

Nephrogenic diabetes insipidus (NDI) is characterized by renal tubular resistance to the antidiuretic effect of arginine vasopressin (AVP). NDI may be inherited as an autosomal dominant or X-linked recessive disorder. The autosomal dominant form of NDI results from mutations of the aquaporin 2 gene (AQP2). AQP2 encodes a water channel of the renal collecting duct. Its disruption causes autosomal dominant NDI (113,114) and occasionally recessive forms of the disease. 

Aquaporins help water to pass through biological membranes. They form hydrophilic pores that allow H2O molecules, but not hydrated ions or larger molecules, to pass through. Aquaporins are particularly important in the kidney, where they promote the reuptake of water (see p. 328). Aquaporin-2 in the renal collecting ducts is regulated by antidiuretic hormone (ADH, vasopressin), which via cAMP leads to shifting of the channels from the ER into the plasma membrane. 

Bai C, Fukuda N, Song Y, Ma T, Matthay MA, Verkman AS (1999) Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice. 1 CUn Invest 103 555—561 Berry V, Francis P, Kaushal S, Moore A, Bhattacharya S (2000) Missense mutations in MIP underUe autosomal dominant polymorphic and lamellar cataracts linked to 12q. Nat Genet 25 15—17 Binder DK, Oshio K, Ma T, Verkman AS, Manley GT (2004) Increased seizure threshold in mice lacking aquaporin-4 water channels. Neuroreport 15 259—262... 

Condeelis J (1993) Life at the leading edge the formation of cell protrusions. Annu Rev Cell Biol 9 411 44 Da T, Verkman AS (2004) Aquaporin-4 gene disruption in mice protects against impaired retinal function and cell death after ischemia. Invest Ophthalmol Vis Sci 45 4477 483 Deen PM, Verdijk MA, Knoers NV, Wieringa B, Monnens LA, van Os CH, van Oost BA (1994) Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine. Science 264 92-95... 

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