Abstract
Abstract: :
Purpose: Calcium–activated chloride currents modulate neuron and muscle excitability, synaptic transmission, and fluid flux in epithelia. Members of the recently identified ClCa family of chloride channels have been shown to produce calcium–activated chloride currents (ICl(Ca)) in heterologous systems, and may participate in ICl(Ca) seen in ocular tissues. Several ocular tissues including cornea, retina, and retinal pigment epithelium (RPE) have ICl(Ca)s. In corneal epithelium, secretion of chloride from the stroma to the tears leads to an osmotically–coupled fluid transport necessary to maintain corneal clarity. A prominent ICl(Ca) is present in photoreceptor terminals, which has direct effects on calcium current (ICa) and membrane potential, thus influencing synaptic transmission. In addition, ICl(Ca) is present in the basolateral membrane of the RPE. This current helps maintain proper secretory activity from the vitreous to the choroid. To get a more comprehensive distribution analysis of eye, we examined the expression of ClCa isoforms in ocular tissues. Methods: Two new ClCas, mClCa5 and mClCa6, were cloned from eye and intestine respectively. Tissue distribution was determined by RT–PCR. Results:mClCa1 and/or mClCa2 and a mClCa1 splice variant showed expression in cornea, retina, and RPE, with the highest level in cornea. mClCa3 was specific to retina, and mClCa4 was specific to cornea. mClCa5 showed expression in all three ocular tissues, with very high levels in cornea, and trace levels in retina. mClCa6 and a splice variant were present in cornea and RPE. Wild type mClCa6 showed greater expression than splice variant in cornea, while the opposite was true in RPE. Conclusions: These data support an important role for ClCas in eye, and they may contribute to ICl(Ca) in cornea, retina, and RPE.
Keywords: ion channels • ion channels • gene/expression