Mutation of a NCKX Eliminates Glial Microdomain Calcium Oscillations and Enhances Seizure Susceptibility
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[s...
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| Format: | Article |
| Language: | en_US |
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Society for Neuroscience
2013
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| Online Access: | http://hdl.handle.net/1721.1/80313 https://orcid.org/0000-0001-5576-2887 |
| _version_ | 1826217596321529856 |
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| author | Melom, Jan Elizabeth Littleton, J. Troy |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Melom, Jan Elizabeth Littleton, J. Troy |
| author_sort | Melom, Jan Elizabeth |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T17:06:11Z |
| format | Article |
| id | mit-1721.1/80313 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:06:11Z |
| publishDate | 2013 |
| publisher | Society for Neuroscience |
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| spelling | mit-1721.1/803132022-09-29T23:40:34Z Mutation of a NCKX Eliminates Glial Microdomain Calcium Oscillations and Enhances Seizure Susceptibility Melom, Jan Elizabeth Littleton, J. Troy Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Melom, Jan Elizabeth Littleton, J. Troy 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. National Institutes of Health (U.S.) (NIH Grant NS43244) National Institutes of Health (U.S.) (NIH grant F31NS076024) 2013-08-29T20:04:25Z 2013-08-29T20:04:25Z 2013-01 2012-10 Article http://purl.org/eprint/type/JournalArticle 0270-6474 1529-2401 http://hdl.handle.net/1721.1/80313 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. https://orcid.org/0000-0001-5576-2887 en_US http://dx.doi.org/10.1523/jneurosci.3920-12.2013 Journal of Neuroscience Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Society for Neuroscience SFN |
| spellingShingle | Melom, Jan Elizabeth Littleton, J. Troy Mutation of a NCKX Eliminates Glial Microdomain Calcium Oscillations and Enhances Seizure Susceptibility |
| title | Mutation of a NCKX Eliminates Glial Microdomain Calcium Oscillations and Enhances Seizure Susceptibility |
| title_full | Mutation of a NCKX Eliminates Glial Microdomain Calcium Oscillations and Enhances Seizure Susceptibility |
| title_fullStr | Mutation of a NCKX Eliminates Glial Microdomain Calcium Oscillations and Enhances Seizure Susceptibility |
| title_full_unstemmed | Mutation of a NCKX Eliminates Glial Microdomain Calcium Oscillations and Enhances Seizure Susceptibility |
| title_short | Mutation of a NCKX Eliminates Glial Microdomain Calcium Oscillations and Enhances Seizure Susceptibility |
| title_sort | mutation of a nckx eliminates glial microdomain calcium oscillations and enhances seizure susceptibility |
| url | http://hdl.handle.net/1721.1/80313 https://orcid.org/0000-0001-5576-2887 |
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