Role of ion channels in aqueous humor formation

The aqueous humor is secreted by the ciliary epithelium, a bilayered syncytial epithelium comprising a pigmented (PE) cell layer abutting the stroma and a nonpigmented (NPE) cell layer facing the aqueous phase. As in other epithelia, secretion depends on the transfer of solute, with water passively following. Na+, K+, and Cl- enter the syncytium principally through a Na(+)-K(+)-2Cl- symport, diffusing to the aqueous surface of the NPE cells. The Na+, K+, and Cl- are secreted into the aqueous humor through the Na+/K+ exchange pump, K+ channels, and Cl- channels, respectively. Na+ is also secreted between the cells in response to a small transepithelial potential. The K+ channels are critical not only for K+ release but also for hyperpolarizing the membrane, providing an electrical driving force for Cl- secretion. Some of the K+ channels are Ca2+ sensitive and can be activated by Ca2+ entry through T- and L-type Ca2+ channels. The roles of the ciliary epithelial nonselective and Na+ channels are less clear. This review describes the ion channels thus far identified in the ciliary epithelium in terms of the activation and inactivation of their macroscopic currents, the open probabilities and conductances of the single channels, and their locations and regulation. The review relates each class of channel to known families of channels and indicates how those channels can contribute to the secretion of the aqueous humor.