Human AQP1 is a constitutively open channel that closes by a membrane tension-mediated mechanism

MARCELO OZU; RICARDO A. DORR; FACUNDO GUTIERREZ; M. TERESA POLITI; ROXANA TORIANO

BIOPHYSICAL JOURNAL

CELL PRESS

Lugar: United States; Año: 2013 vol. 104 p. 85 - 95

0006-3495

This work presents experimental results combined with model-dependent predictions on 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 then 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, 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.