carbenoxolone blocks the light-evoked rise in intracellular calcium in isolated melanopsin ganglion cell photoreceptors生胃酮块light-evoked上升在孤立的视网膜神经节细胞胞内钙感光层.pdfVIP

Carbenoxolone Blocks the Light-Evoked Rise in Intracellular Calcium in Isolated Melanopsin Ganglion Cell Photoreceptors Jayne R. Bramley, Erin M. Wiles, Patricia J. Sollars, Gary E. Pickard* School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, Nebraska, United States of America Abstract Background: Retinal ganglion cells expressing the photopigment melanopsin are intrinsically photosensitive (ipRGCs). These ganglion cell photoreceptors send axons to several central targets involved in a variety of functions. Within the retina ipRGCs provide excitatory drive to dopaminergic amacrine cells via glutamatergic signals and ipRGCs are coupled to wide- field GABAergic amacrine cells via gap junctions. However, the extent to which ipRGCs are coupled to other retinal neurons in the ganglion cell layer via gap junctions is unclear. Carbenoxolone, a widely employed gap junction inhibitor, greatly reduces the number of retinal neurons exhibiting non-rod, non-cone mediated light-evoked Ca2+ signals suggesting extensive intercellular coupling between ipRGCs and non-ipRGCs in the ganglion cell layer. However, carbenoxolone may directly inhibit light-evoked Ca2+ signals in ipRGCs independent of gap junction blockade. Methodology/Principal Findings: To test the possibility that carbenoxolone directly inhibits light-evoked Ca2+ responses in ipRGCs, the light-evoked rise in intracellular Ca2+ ([Ca2+] ) was examined using fura-2 imaging in isolated rat ipRGCs i maintained in short-term culture in the absence and presence of carbenoxolone. Carbenoxolone at 50 and 100 mM concentrations completely abolished the light-evoked ris