title: Mutation of a NCKX eliminates glial microdomain calcium oscillations and enhances seizure susceptibility.
abstract: Glia exhibit spontaneous and activity-dependent fluctuations in intracellular Ca(2+), yet it is unclear whether glial Ca(2+) oscillations are required during neuronal signaling. Somatic glial Ca(2+) waves are primarily mediated by the release of intracellular Ca(2+) stores, and their relative importance in normal brain physiology has been disputed. Recently, near-membrane microdomain Ca(2+) transients were identified in fine astrocytic processes and found to arise via an intracellular store-independent process. Here, we describe the identification of rapid, near-membrane Ca(2+) oscillations in Drosophila cortex glia of the CNS. In a screen for temperature-sensitive conditional seizure mutants, we identified a glial-specific Na(+)/Ca(2+), K(+) exchanger (zydeco) that is required for microdomain Ca(2+) oscillatory activity. We found that zydeco mutant animals exhibit increased susceptibility to seizures in response to a variety of environmental stimuli, and that zydeco is required acutely in cortex glia to regulate seizure susceptibility. We also found that glial expression of calmodulin is required for stress-induced seizures in zydeco mutants, suggesting a Ca(2+)/calmodulin-dependent glial signaling pathway underlies glial-neuronal communication. These studies demonstrate that microdomain glial Ca(2+) oscillations require NCKX-mediated plasma membrane Ca(2+) flux, and that acute dysregulation of glial Ca(2+) signaling triggers seizures.
authors: Picower Institute for Learning and Memory, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors: Jan E
authors: JE
authors: Melom
authors: J Troy
authors: JT
authors: Littleton
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster; D020022:Genetic Predisposition to Disease; D009154:Mutation; D009457:Neuroglia / Q000378:metabolism*; D012640:Seizures / Q000235:genetics* / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D019831:Sodium-Calcium Exchanger; D002118:Calcium