L-type Ca 2+ channels mediate regulation of glutamate release by subthreshold potential changes

What is it about?

Neuronal action potentials lead to the release of neurotransmitters, called synaptic transmission. It has been known that various factors can modulate the process of synaptic transmission at nerve terminals. However, it is less explored whether subthreshold potential and its change also control synaptic transmission. If so, what are the responsible molecular players in this regard? Our study, the article “L-type Ca2+ channels mediate regulation of glutamate release by subthreshold potential changes” demonstrated that subthreshold shift in the resting membrane potential modulates synaptic transmission via L-type Ca2+ channel and calmodulin-mediate Ca2+ signaling. More specifically, we demonstrate that subthreshold depolarization induces the increase of basal Ca2+ level at synapses via L-type Ca2+ channels, and enhances both spontaneous and evoked release in primary cultured hippocampal neurons and CA3 pyramidal neurons. Furthermore, Intracellular Ca2+ modulation by treating EGTA-AM, a Ca2+ chelator, and inhibition of calmodulin discontinue subthreshold depolarization-dependent facilitation of neurotransmission and L-type Ca2+ channel-mediated modulation of neurotransmission. In summary, our study provides the mechanistic insight that subthreshold potential change regulates neurotransmitter release and highlights the role of L-type Ca2+ channel in this regulation.

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Photo by Hal Gatewood on Unsplash

Photo by Hal Gatewood on Unsplash

Why is it important?

Modulation of neurotransmitter release at nerve terminals is one of the most essential processes for brain function. Although there are various studies on modulatory factors of synaptic transmission, how subthreshold depolarization affects the regulation of transmitter release is less known. In this study, we found subthreshold potential changes have influenced basal Ca2+ level via L-type Ca2+ channel, which activates Ca2+-mediate signaling such as calmodulin, increases the size of readily releasable pool and the release probability, and eventually increases the spontaneous release and evoked release of glutamate. This study provides mechanistic insight into how subthreshold potential changes contribute to controlling neurotransmission.