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- Title
Conditional Knockout of Neurexins Alters the Contribution of Calcium Channel Subtypes to Presynaptic Ca 2+ Influx.
- Authors
Brockhaus, Johannes; Kahl, Iris; Ahmad, Mohiuddin; Repetto, Daniele; Reissner, Carsten; Missler, Markus
- Abstract
Presynaptic Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) is a key signal for synaptic vesicle release. Synaptic neurexins can partially determine the strength of transmission by regulating VGCCs. However, it is unknown whether neurexins modulate Ca2+ influx via all VGCC subtypes similarly. Here, we performed live cell imaging of synaptic boutons from primary hippocampal neurons with a Ca2+ indicator. We used the expression of inactive and active Cre recombinase to compare control to conditional knockout neurons lacking either all or selected neurexin variants. We found that reduced total presynaptic Ca2+ transients caused by the deletion of all neurexins were primarily due to the reduced contribution of P/Q-type VGCCs. The deletion of neurexin1α alone also reduced the total presynaptic Ca2+ influx but increased Ca2+ influx via N-type VGCCs. Moreover, we tested whether the decrease in Ca2+ influx induced by activation of cannabinoid receptor 1 (CB1-receptor) is modulated by neurexins. Unlike earlier observations emphasizing a role for β-neurexins, we found that the decrease in presynaptic Ca2+ transients induced by CB1-receptor activation depended more strongly on the presence of α-neurexins in hippocampal neurons. Together, our results suggest that neurexins have unique roles in the modulation of presynaptic Ca2+ influx through VGCC subtypes and that different neurexin variants may affect specific VGCCs.
- Subjects
CALCIUM ions; NEUREXINS; CALCIUM channels; CANNABINOID receptors; SYNAPTIC vesicles; CELL imaging; NEURAL transmission; RECOMBINASES; AMPA receptors
- Publication
Cells (2073-4409), 2024, Vol 13, Issue 11, p981
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells13110981