The tight temporal and spatial control of calcium signalling in subcellular domains is an essential feature for neuronal activity and thus brain function. Subcellular structures as synapses or membrane contacts between the plasma membrane (PM) and the endoplasmatic reticulum (ER) are populated by calcium conducting and calcium sensing molecules to trigger and control inter- and intracellular communication.

Within synapses voltage gated calcium channels (VGCC) in the presynaptic membrane are tightly linked to a pool of synaptic vesicles. Despite the well-defined function of VGCC within the process of transmitter vesicle release and vesicle recycling, the mechanisms how VGCC are recruited, stabilized and maintained within the presynaptic membrane is still unclear. The use of a single molecule imaging approach uncovered that VGCC show a surprising high dynamic organisation within the presynaptic membrane. This suggest that not only channel kinetics but also the fluctuation of local channel numbers within the presynaptic membrane contribute to the release property of a synapse.

Despite VGCC have predominant function within the synapse, there is strong evidence that other calcium channels contribute to synaptic plasticity as well. Particular ORAI channels in the PM and STIM proteins in the ER forming the so-called store operated calcium channels (SOC). This complex is known as highly dynamic calcium conducting module, which forms in an activity dependent manner. Using the power of single molecule tracking we probed whether STIM proteins can be used as an indicator whether SOCs are enriched in synapses. Tracking STIM proteins within the ER membrane show a very heterogenous dynamic organisation, but no specific confinement within synapses. Even after strong depletion of intracellular calcium stores, STIM proteins do not enter the synaptic compartment.

The dynamic organisation of calcium conducting proteins propose that calcium channels in subcellular compartments are highly variable and let hypothesis that a change in number and density of calcium channels contribute to the plasticity of synapses.

Or online: Click here