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PMID: 12968005 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Modulation of synaptic transmission by the BCL-2 family protein BCL-xL.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 23 ·No. 23 ·2003-09-10 ·Pages 8423-31

Jonas EA, Hoit D, Hickman JA, Brandt TA, Polster BM, Fannjiang Y, McCarthy E, Montanez MK, Hardwick JM, Kaczmarek LK

Abstract

BCL-2 family proteins are known to regulate cell death during development by influencing the permeability of mitochondrial membranes. The anti-apoptotic BCL-2 family protein BCL-xL is highly expressed in the adult brain and localizes to mitochondria in the presynaptic terminal of the adult squid stellate ganglion. Application of recombinant BCL-xL through a patch pipette to mitochondria inside the giant presynaptic terminal triggered multiconductance channel activity in mitochondrial membranes. Furthermore, injection of full-length BCL-xL protein into the presynaptic terminal enhanced postsynaptic responses and enhanced the rate of recovery from synaptic depression, whereas a recombinant pro-apoptotic cleavage product of BCL-xL attenuated postsynaptic responses. The effect of BCL-xL on synaptic responses persisted in the presence of a blocker of mitochondrial calcium uptake and was mimicked by injection of ATP into the terminal. These studies indicate that the permeability of outer mitochondrial membranes influences synaptic transmission, and they raise the possibility that modulation of mitochondrial conductance by BCL-2 family proteins affects synaptic stability.

MeSH Terms
Adenosine Triphosphate/pharmacology Animals Coloring Agents/pharmacology Decapodiformes Electric Stimulation/methods In Vitro Techniques Ion Channels/metabolism Long-Term Synaptic Depression/drug effects,physiology Mitochondria/drug effects,metabolism Neurons/drug effects,metabolism,physiology Proto-Oncogene Proteins c-bcl-2/pharmacology,physiology Recovery of Function/drug effects,physiology Ruthenium Red/pharmacology Synaptic Transmission/drug effects,physiology bcl-X Protein
Chemicals
Coloring Agents Ion Channels Proto-Oncogene Proteins c-bcl-2 bcl-X Protein Ruthenium Red Adenosine Triphosphate
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Jonas Elizabeth A
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06250, USA.
Hoit Daniel
Hickman John A
Brandt Teresa A
Polster Brian M
Fannjiang Yihru
McCarthy Erin
Montanez Marlena K
Hardwick J Marie
Kaczmarek Leonard K
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2003-09-10
Pages
8423-31
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6740692
Subset
IM
Grants
NINDS NIH HHS · R01 NS018492 · United States
NINDS NIH HHS · NS 18492 · United States
NINDS NIH HHS · NS 34702 · United States
External Links
PubMed source PMC Full Text View journal details
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