| First Author | Geisler SM | Year | 2025 |
| Journal | Neuroscience | Volume | 580 |
| Pages | 169-180 | PubMed ID | 40543890 |
| Mgi Jnum | J:375171 | Mgi Id | MGI:8220648 |
| Doi | 10.1016/j.neuroscience.2025.06.039 | Citation | Geisler SM, et al. (2025) Stable expression of voltage-gated calcium channel mRNA in alpha(2)delta (CACNA2D) knockout mouse brains. Neuroscience 580:169-180 |
| abstractText | Voltage-gated Ca(2+) channels (VGCCs) regulate Ca(2+) entry in healthy and diseased neurons, and their function is modulated by auxiliary alpha(2)delta subunits. Among the four alpha(2)delta isoforms, alpha(2)delta-1, alpha(2)delta-2, and alpha(2)delta-3 show overlapping expression in various brain regions, raising questions about their respective specific and redundant roles. Here, we investigated if the loss of alpha(2)delta isoforms affects mRNA expression of other VGCC alpha(1), alpha(2)delta, and beta subunits. Moreover, qPCR expression profiling in knockout conditions provides insights into potential compensatory mechanisms. To this end, we analyzed the expression of the high-VGCC complement, including seven alpha(1), four beta, and four alpha(2)delta subunit isoforms, in hippocampal and striatal tissues from alpha(2)delta single and alpha(2)delta-1/-3 double knockout mice. Our findings reveal that mRNA expression profiles of hippocampal and striatal tissues contain the entire set of neuronal high-VGCC subunits. Notably, alpha(2)delta-3 mRNA is the most abundant isoform in striatum and alpha(2)delta-1/-3 double knockout mice show increased amounts of mutant alpha(2)delta-3 mRNA reporter transcripts compared to alpha(2)delta-3 single knockout mice. These findings support a critical role of alpha(2)delta-3 in GABAergic striatal medium spiny neurons. Of note, mRNA expression levels of individual alpha(1) and beta isoforms were remarkably similar between alpha(2)delta single knockout and alpha(2)delta-1/-3 double knockout compared to control mice. Taken together, our study provides novel insights into the resilience of VGCC mRNA levels to disruptions of alpha(2)delta isoform expression, suggesting transcriptional stability of core calcium channel components comparable to housekeeping genes. However, this stability does not fully prevent physiological deficits, suggesting limited functional compensation at the transcript level. |
