title: Human AQP1 is a constitutively open channel that closes by a membrane-tension-mediated mechanism.
abstract: This work presents experimental results combined with model-dependent predictions regarding the osmotic-permeability regulation of human aquaporin 1 (hAQP1) expressed in Xenopus oocyte membranes. Membrane elastic properties were studied under fully controlled conditions to obtain a function that relates internal volume and pressure. This function was used to design a model in which osmotic permeability could be studied as a pressure-dependent variable. The model states that hAQP1 closes with membrane-tension increments. It is important to emphasize that the only parameter of the model is the initial osmotic permeability coefficient, which was obtained by model-dependent fitting. The model was contrasted with experimental records from emptied-out Xenopus laevis oocytes expressing hAQP1. Simulated results reproduce and predict volume changes in high-water-permeability membranes under hypoosmotic gradients of different magnitude, as well as under consecutive hypo- and hyperosmotic conditions. In all cases, the simulated permeability coefficients are similar to experimental values. Predicted pressure, volume, and permeability changes indicate that hAQP1 water channels can transit from a high-water-permeability state to a closed state. This behavior is reversible and occurs in a cooperative manner among monomers. We conclude that hAQP1 is a constitutively open channel that closes mediated by membrane-tension increments.
authors: Laboratorio de Biomembranas, Departamento de Ciencias Fisiológicas, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. mozu@fmed.uba.ar
authors: Marcelo
authors: M
authors: Ozu
authors: Ricardo A
authors: RA
authors: Dorr
authors: Facundo
authors: F
authors: Gutiérrez
authors: M Teresa
authors: MT
authors: Politi
authors: Roxana
authors: R
authors: Toriano
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology*; D003198:Computer Simulation; D004548:Elasticity; D006096:Gramicidin / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating; D008954:Models, Biological; D009865:Oocytes / Q000502:physiology; D009995:Osmosis; D013500:Surface Tension; D014982:Xenopus laevis
chemical_list: C496020:AQP1 protein, human; D006096:Gramicidin; D051398:Aquaporin 1