RT Journal Article
SR Electronic
T1 Mutation of a NCKX Eliminates Glial Microdomain Calcium Oscillations and Enhances Seizure Susceptibility
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1169
OP 1178
DO 10.1523/JNEUROSCI.3920-12.2013
VO 33
IS 3
A1 Jan E. Melom
A1 J. Troy Littleton
YR 2013
UL http://www.jneurosci.org/content/33/3/1169.abstract
AB Glia exhibit spontaneous and activity-dependent fluctuations in intracellular Ca2+, yet it is unclear whether glial Ca2+ oscillations are required during neuronal signaling. Somatic glial Ca2+ waves are primarily mediated by the release of intracellular Ca2+ stores, and their relative importance in normal brain physiology has been disputed. Recently, near-membrane microdomain Ca2+ 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 Ca2+ oscillations in Drosophila cortex glia of the CNS. In a screen for temperature-sensitive conditional seizure mutants, we identified a glial-specific Na+/Ca2+, K+ exchanger (zydeco) that is required for microdomain Ca2+ 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 Ca2+/calmodulin-dependent glial signaling pathway underlies glial–neuronal communication. These studies demonstrate that microdomain glial Ca2+ oscillations require NCKX-mediated plasma membrane Ca2+ flux, and that acute dysregulation of glial Ca2+ signaling triggers seizures.