TY - JOUR T1 - Modulation of Synaptic Transmission by the BCL-2 Family Protein BCL-xL JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8423 LP - 8431 DO - 10.1523/JNEUROSCI.23-23-08423.2003 VL - 23 IS - 23 AU - Elizabeth A. Jonas AU - Daniel Hoit AU - John A. Hickman AU - Teresa A. Brandt AU - Brian M. Polster AU - Yihru Fannjiang AU - Erin McCarthy AU - Marlena K. Montanez AU - J. Marie Hardwick AU - Leonard K. Kaczmarek Y1 - 2003/09/10 UR - http://www.jneurosci.org/content/23/23/8423.abstract N2 - 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. ER -