RT Journal Article
SR Electronic
T1 Calmodulin Bidirectionally Regulates Evoked and Spontaneous Neurotransmitter Release at Retinal Ribbon Synapses
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0257-20.2020
DO 10.1523/ENEURO.0257-20.2020
VO 8
IS 1
A1 Liang, Chao-Qun
A1 Zhang, Gong
A1 Zhang, Lei
A1 Chen, Si-Yun
A1 Wang, Jun-Nan
A1 Zhang, Ting-Ting
A1 Singer, Joshua H.
A1 Ke, Jiang-Bin
YR 2021
UL http://www.eneuro.org/content/8/1/ENEURO.0257-20.2020.abstract
AB For decades, a role for the Ca2+-binding protein calmodulin (CaM) in Ca2+-dependent presynaptic modulation of synaptic transmission has been recognized. Here, we investigated the influence of CaM on evoked and spontaneous neurotransmission at rod bipolar (RB) cell→AII amacrine cell synapses in the mouse retina. Our work was motivated by the observations that expression of CaM in RB axon terminals is extremely high and that [Ca2+] in RB terminals normally rises sufficiently to saturate endogenous buffers, making tonic CaM activation likely. Taking advantage of a model in which RBs can be stimulated by expressed channelrhodopsin-2 (ChR2) to avoid dialysis of the presynaptic terminal, we found that inhibition of CaM dramatically decreased evoked release by inhibition of presynaptic Ca channels while at the same time potentiating both Ca2+-dependent and Ca2+-independent spontaneous release. Remarkably, inhibition of myosin light chain kinase (MLCK), but not other CaM-dependent targets, mimicked the effects of CaM inhibition on evoked and spontaneous release. Importantly, initial antagonism of CaM occluded the effect of subsequent inhibition of MLCK on spontaneous release. We conclude that CaM, by acting through MLCK, bidirectionally regulates evoked and spontaneous release at retinal ribbon synapses.