Localization and dynamics of voltage-gated calcium channels in axons of cultured hippocampal neurons
left: Expression of mEOS3.2-tagged CaV2.1 channels within axons (gray puncta) and encircled synaptic areas (magenta) are shown.
center: Resulting from sptPALM experiments the trajectories of individual CaV2.1 channels along the axonal membranes are shown.
right: The calculated diffusion map of the CaV2.1 channels allow to localize individual confinement areas shown as energy wells (see Heck et al. 2019).
Calcium channel dynamics within the neuronal membrane
The communication via chemical synapses is initiated by vesicular release of neurotransmitters - a process triggered by the transient influx of calcium ions mainly through voltage-gated calcium channels (VGCCs).
For successful induction of vesicle exocytosis, the local distance between VGCCs and vesicular calcium sensors is essential to trigger transmitter release.
Since the synapse is a highly dynamic compartment constantly reorganizing the molecules involved in neurotransmission, we are interested in the meaning of VGCCs’ lateral mobility, which might impact on the function of VGCCs, beside their biophysical properties, and alter synaptic transmission and plasticity.
Alternative splice variants of calcium channels, which exhibit a different affinity to intracellular scaffold proteins and synaptic vesicles, suggest a different anchoring of channels within signaling complexes. Here, a particular C-terminal splice variant has been already in focus of research in context with the clinical manifestation of the channelopathy SCA6.
We have developed optogenetic approaches to reversibly disturb local calcium channel organization and monitor the functional consequences. By investigating VGCC surface dynamics and the distinct expression profiles of calcium channel splice variants we aim to uncover the impact of channel dynamics for the computational power of individual synapses and their impact in neuronal network activity.
Related publications:
Heck J, Parutto P, Ciuraszkiewicz A, Bikbaev A, Freund R, Mitlöhner J, Alonso M, Fejtova A, Holcman D, Heine M (2019)
Transient confinement of CaV2.1 Ca2+-channel splice variants shapes synaptic short-term plasticity. Neuron 103(1): 66-79. https://doi.org/10.1016/j.neuron.2019.04.030
Schneider R, Hosy E, Kohl J, Klyueva Y, Choquet D, Thomas U, Voigt A, Heine M (2015)
Mobility of calcium channels in the presynaptic membrane. Neuron 86(3): 672-79. https://doi.org/10.1016/j.neuron.2015.03.050