title: The influence of sodium-calcium exchange inhibitors on rabbit lens ion balance and transparency.
abstract: Calcium regulation is essential to the maintenance of lens transparency. To maintain cytoplasmic calcium concentration at the required low level the lens must export calcium continuously. Here, studies were conducted to test whether sodium-calcium exchanger (NCX) inhibitors disturb calcium balance in the rabbit lens. Intact lenses were incubated up to 48 h in the presence or absence of the NCX inhibitor bepridil. Lens sodium, potassium and calcium content were determined by atomic absorption spectrophotometry. Fluo-4 was used to measure epithelial cell cytoplasmic calcium concentration in an intact lens preparation. NCX1 protein expression in lens epithelium was examined by western blot. NCX1 band density was similar in central and equatorial epithelium samples. Lenses exposed to bepridil (30 microM) lost transparency at the anterior and exhibited significant changes in electrolyte and water content. After 48 h, lens calcium content more than doubled, sodium increased four fold and potassium was significantly reduced. In contrast, lenses exposed to inhibitors of reverse mode calcium transport by NCX (KBR7943 or SN-6) remained transparent and the electrolyte and water content of the lens remained unchanged. The ability of bepridil to cause significant changes in lens transparency and electrolyte content points to an important role for NCX-meditated calcium export in the lens.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Louisville, School of Medicine, Louisville, KY 40202, USA.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Tamiya
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Delamere
mesh_terms: D000818:Animals; D001593:Benzyl Compounds / Q000494:pharmacology; D015764:Bepridil / Q000494:pharmacology; D002118:Calcium / Q000032:analysis; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005136:Eye Proteins / Q000032:analysis; D017136:Ion Transport / Q000187:drug effects; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques / Q000379:methods; D011188:Potassium / Q000032:analysis; D011817:Rabbits; D012964:Sodium / Q000032:analysis; D019831:Sodium-Calcium Exchanger / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000187:drug effects; D053778:Thiazolidines / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; C487681:2-(4-(4-nitrobenzyloxy)benzyl)thiazolidine-4-carboxylic acid ethyl ester; D001593:Benzyl Compounds; D002121:Calcium Channel Blockers; D005136:Eye Proteins; D019831:Sodium-Calcium Exchanger; D053778:Thiazolidines; C110374:sodium-calcium exchanger 1; D015764:Bepridil; D012964:Sodium; D013890:Thiourea; D011188:Potassium; D002118:Calcium