title: Calcium homeostasis and cone signaling are regulated by interactions between calcium stores and plasma membrane ion channels.
abstract: Calcium is a messenger ion that controls all aspects of cone photoreceptor function, including synaptic release. The dynamic range of the cone output extends beyond the activation threshold for voltage-operated calcium entry, suggesting another calcium influx mechanism operates in cones hyperpolarized by light. We have used optical imaging and whole-cell voltage clamp to measure the contribution of store-operated Ca(2+) entry (SOCE) to Ca(2+) homeostasis and its role in regulation of neurotransmission at cone synapses. Mn(2+) quenching of Fura-2 revealed sustained divalent cation entry in hyperpolarized cones. Ca(2+) influx into cone inner segments was potentiated by hyperpolarization, facilitated by depletion of intracellular Ca(2+) stores, unaffected by pharmacological manipulation of voltage-operated or cyclic nucleotide-gated Ca(2+) channels and suppressed by lanthanides, 2-APB, MRS 1845 and SKF 96365. However, cation influx through store-operated channels crossed the threshold for activation of voltage-operated Ca(2+) entry in a subset of cones, indicating that the operating range of inner segment signals is set by interactions between store- and voltage-operated Ca(2+) channels. Exposure to MRS 1845 resulted in approximately 40% reduction of light-evoked postsynaptic currents in photopic horizontal cells without affecting the light responses or voltage-operated Ca(2+) currents in simultaneously recorded cones. The spatial pattern of store-operated calcium entry in cones matched immunolocalization of the store-operated sensor STIM1. These findings show that store-operated channels regulate spatial and temporal properties of Ca(2+) homeostasis in vertebrate cones and demonstrate their role in generation of sustained excitatory signals across the first retinal synapse.
authors.affiliation: Department of Ophthalmology, University of California San Francisco School of Medicine, San Francisco, California, United States of America.
authors.forename: Tamas
authors.initials: T
authors.lastname: Szikra
authors.forename: Peter
authors.initials: P
authors.lastname: Barabas
authors.forename: Theodore M
authors.initials: TM
authors.lastname: Bartoletti
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Abram
authors.initials: A
authors.lastname: Akopian
authors.forename: Wallace B
authors.initials: WB
authors.lastname: Thoreson
authors.forename: David
authors.initials: D
authors.lastname: Krizaj
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006706:Homeostasis; D007473:Ion Channels / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D007473:Ion Channels; D002118:Calcium
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