Modulation of synaptic transmission by the BCL-2 family protein BCL-xL.
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.
Jonas
Elizabeth A
EA
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06250, USA.
Hoit
Daniel
D
Hickman
John A
JA
Brandt
Teresa A
TA
Polster
Brian M
BM
Fannjiang
Yihru
Y
McCarthy
Erin
E
Montanez
Marlena K
MK
Hardwick
J Marie
JM
Kaczmarek
Leonard K
LK
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D004396:Coloring Agents / Q000494:pharmacology; D049832:Decapodiformes; D004558:Electric Stimulation / Q000379:methods; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology / Q000502:physiology*; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D012430:Ruthenium Red / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D051020:bcl-X Protein
D004396:Coloring Agents; D007473:Ion Channels; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D012430:Ruthenium Red; D000255:Adenosine Triphosphate