Mutation of a NCKX Eliminates Glial Microdomain Calcium Oscillations and Enhances Seizure Susceptibility
Author(s)Melom, Jan Elizabeth; Littleton, J. Troy
MetadataShow full item record
Glia exhibit spontaneous and activity-dependent fluctuations in intracellular Ca[superscript 2+], yet it is unclear whether glial Ca[superscript 2+] oscillations are required during neuronal signaling. Somatic glial Ca[superscript 2+] waves are primarily mediated by the release of intracellular Ca[superscript 2+] stores, and their relative importance in normal brain physiology has been disputed. Recently, near-membrane microdomain Ca[superscript 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[superscript 2+] oscillations in Drosophila cortex glia of the CNS. In a screen for temperature-sensitive conditional seizure mutants, we identified a glial-specific Na[superscript +]/Ca[superscript 2+], K[superscript +] exchanger (zydeco) that is required for microdomain Ca[superscript 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[superscript 2+]/calmodulin-dependent glial signaling pathway underlies glial–neuronal communication. These studies demonstrate that microdomain glial Ca[superscript 2+] oscillations require NCKX-mediated plasma membrane Ca[superscript 2+] flux, and that acute dysregulation of glial Ca[superscript 2+] signaling triggers seizures.
DepartmentMassachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Picower Institute for Learning and Memory
Journal of Neuroscience
Society for Neuroscience
Melom, J. E., and J. T. Littleton. “Mutation of a NCKX Eliminates Glial Microdomain Calcium Oscillations and Enhances Seizure Susceptibility.” Journal of Neuroscience 33, no. 3 (January 16, 2013): 1169-1178.
Final published version