The extracellular calcium-sensing receptor (CaR) confers the capacity to sense small changes in the extracellular Ca2+ concentration (Ca2+o) not only upon cells involved in maintaining systemic Ca2+ homeostasis but also upon those not directly involved in this process. Since high Ca2+o is known to affect various physiological processes in lens epithelium both in health and in disease states (e.g., the formation of cataracts in hypocalcemic states), we investigated the expression and function of the CaR in these cells. By RT-PCR and immunocytochemistry the CaR is expressed in human lens epithelial cells in culture. In addition, the open state probability of a Ca(2+)-activated potassium (K+) channel with a conductance of 82 +/- 3 pS is significantly increased by elevating Ca2+o to 3.0 mM or by application of 100 microM neomycin, both effective CaR agonists. Therefore, our data suggest that human lens-epithelial cells express the CaR, which may be functionally linked to Ca(2+)-activated K+ channels and, perhaps, to other ion channels involved in ionic homeostasis in the lens.