PT  - JOURNAL ARTICLE
AU  - Chao-Qun Liang
AU  - Gong Zhang
AU  - Lei Zhang
AU  - Si-Yun Chen
AU  - Jun-Nan Wang
AU  - Ting-Ting Zhang
AU  - Joshua H. Singer
AU  - Jiang-Bin Ke
TI  - Calmodulin Bidirectionally Regulates Evoked and Spontaneous Neurotransmitter Release at Retinal Ribbon Synapses
AID  - 10.1523/ENEURO.0257-20.2020
DP  - 2021 Jan 01
TA  - eneuro
PG  - ENEURO.0257-20.2020
VI  - 8
IP  - 1
4099  - http://www.eneuro.org/content/8/1/ENEURO.0257-20.2020.short
4100  - http://www.eneuro.org/content/8/1/ENEURO.0257-20.2020.full
SO  - eNeuro2021 Jan 01; 8
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.