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Presynaptic homeostasis at CNS nerve terminals compensates for lack of a key Ca2+ entry pathway.

Publication ,  Journal Article
Piedras-Rentería, ES; Pyle, JL; Diehn, M; Glickfeld, LL; Harata, NC; Cao, Y; Kavalali, ET; Brown, PO; Tsien, RW
Published in: Proc Natl Acad Sci U S A
March 9, 2004

At central synapses, P/Q-type Ca(2+) channels normally provide a critical Ca(2+) entry pathway for neurotransmission. Nevertheless, we found that nerve terminals lacking alpha(1A) (Ca(V)2.1), 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 alpha(1A) (-/-) mice. First, the presynaptic response to an ionophore-mediated Ca(2+) elevation was 50% greater, indicating an enhanced Ca(2+) sensitivity of the release machinery. Second, basal miniature excitatory postsynaptic current frequency in alpha(1A) (-/-) 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 alpha(1A) (-/-) 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 alpha(1A) (-/-) 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 Ca(2+)-sensing molecules were consistent with implications of the direct physiological experiments.

Duke Scholars

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

March 9, 2004

Volume

101

Issue

10

Start / End Page

3609 / 3614

Location

United States

Related Subject Headings

  • RNA, Messenger
  • Presynaptic Terminals
  • Oligonucleotide Array Sequence Analysis
  • Neurons
  • Mice, Knockout
  • Mice
  • Homeostasis
  • Hippocampus
  • Gene Expression Profiling
  • Cyclic AMP-Dependent Protein Kinases
 

Citation

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ICMJE
MLA
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Piedras-Rentería, E. S., Pyle, J. L., Diehn, M., Glickfeld, L. L., Harata, N. C., Cao, Y., … Tsien, R. W. (2004). Presynaptic homeostasis at CNS nerve terminals compensates for lack of a key Ca2+ entry pathway. Proc Natl Acad Sci U S A, 101(10), 3609–3614. https://doi.org/10.1073/pnas.0308188100
Piedras-Rentería, Erika S., Jason L. Pyle, Max Diehn, Lindsey L. Glickfeld, Nobutoshi C. Harata, Yuqing Cao, Ege T. Kavalali, Patrick O. Brown, and Richard W. Tsien. “Presynaptic homeostasis at CNS nerve terminals compensates for lack of a key Ca2+ entry pathway.Proc Natl Acad Sci U S A 101, no. 10 (March 9, 2004): 3609–14. https://doi.org/10.1073/pnas.0308188100.
Piedras-Rentería ES, Pyle JL, Diehn M, Glickfeld LL, Harata NC, Cao Y, et al. Presynaptic homeostasis at CNS nerve terminals compensates for lack of a key Ca2+ entry pathway. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3609–14.
Piedras-Rentería, Erika S., et al. “Presynaptic homeostasis at CNS nerve terminals compensates for lack of a key Ca2+ entry pathway.Proc Natl Acad Sci U S A, vol. 101, no. 10, Mar. 2004, pp. 3609–14. Pubmed, doi:10.1073/pnas.0308188100.
Piedras-Rentería ES, Pyle JL, Diehn M, Glickfeld LL, Harata NC, Cao Y, Kavalali ET, Brown PO, Tsien RW. Presynaptic homeostasis at CNS nerve terminals compensates for lack of a key Ca2+ entry pathway. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3609–3614.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

March 9, 2004

Volume

101

Issue

10

Start / End Page

3609 / 3614

Location

United States

Related Subject Headings

  • RNA, Messenger
  • Presynaptic Terminals
  • Oligonucleotide Array Sequence Analysis
  • Neurons
  • Mice, Knockout
  • Mice
  • Homeostasis
  • Hippocampus
  • Gene Expression Profiling
  • Cyclic AMP-Dependent Protein Kinases