Journal article
Presynaptic homeostasis at CNS nerve terminals compensates for lack of a key Ca2+ entry pathway
Proceedings of the National Academy of Sciences - PNAS, Vol.101(10), pp.3609-3614
03/09/2004
DOI: 10.1073/pnas.0308188100
PMCID: PMC373510
PMID: 14990796
Abstract
At central synapses, P/Q-type Ca2+ channels normally provide a critical Ca2+ entry pathway for neurotransmission. Nevertheless, we found that nerve terminals lacking α1A (CaV2.1), the pore-forming subunit of P/Q-type channels, displayed a remarkable preservation of synaptic function. Two consistent physiological changes reflective of synaptic homeostasis were observed in cultured hippocampal neurons derived from α1A (-/-) mice. First, the presynaptic response to an ionophore-mediated Ca2+ elevation was 50% greater, indicating an enhanced Ca2+ sensitivity of the release machinery. Second, basal miniature excitatory postsynaptic current frequency in α1A (-/-) neurons was increased 2-fold compared with WT neurons and occluded the normal response of presynaptic terminals to cAMP elevation, suggesting that the compensatory mechanism in α1A (-/-) synapses and the modulation of presynaptic function by PKA might share a final common pathway. We used cDNA microarray analysis to identify molecular changes underlying homeostatic regulation in the α1A (-/-) hippocampus. The 40,000 entries in our custom-made array included likely targets of presynaptic homeostasis, along with many other transcripts, allowing a wide-ranging examination of gene expression. The developmental pattern of changes in transcript levels relative to WT was striking; mRNAs at 5 and 11 days postnatal showed little deviation, but clear differences emerged by 22 days. Many of the transcripts that differed significantly in abundance corresponded to known genes that could be incorporated within a logical pattern consistent with the modulation of presynaptic function. Changes in endocytotic proteins, signal transduction kinases, and candidates for Ca2+-sensing molecules were consistent with implications of the direct physiological experiments.
Details
- Title: Subtitle
- Presynaptic homeostasis at CNS nerve terminals compensates for lack of a key Ca2+ entry pathway
- Creators
- Erika S Piedras-Rentería - Department of Molecular and Cellular Physiology, Beckman Center, andJason L Pyle - Department of Molecular and Cellular Physiology, Beckman Center, andMax Diehn - Department of Molecular and Cellular Physiology, Beckman Center, andLindsey L Glickfeld - Department of Molecular and Cellular Physiology, Beckman Center, andNobutoshi C Harata - Department of Molecular and Cellular Physiology, Beckman Center, andYuqing Cao - Department of Molecular and Cellular Physiology, Beckman Center, andEge T Kavalali - Department of Molecular and Cellular Physiology, Beckman Center, andPatrick O Brown - Department of Molecular and Cellular Physiology, Beckman Center, andRichard W Tsien - Department of Molecular and Cellular Physiology, Beckman Center, and
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.101(10), pp.3609-3614
- DOI
- 10.1073/pnas.0308188100
- PMID
- 14990796
- PMCID
- PMC373510
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 03/09/2004
- Academic Unit
- Molecular Physiology and Biophysics
- Record Identifier
- 9984025565602771
Metrics
24 Record Views