Role of voltage-gated L-type calcium channel isoforms for brain function

Striessnig, J., et al. "Role of voltage-gated L-type Ca2+ channel isoforms for brain function." Biochemical Society Transactions 34.Pt 5 (2006): 903-909. This is a more detailed study examining the role of both L-type calcium channel (LTCC) isoforms 1.2 and 1.3 within the brain. Like discussed previously in my last blog, because the LTCC agonist and antagonist do not show specific binding to either 1.2 or 1.3, it has been difficult to differentiate the roles each plays. However, more recently discovered, two groups of genetically modified mice have enabled scientist to conduct much needed studies better characterizing these two calcium channels. The first mouse group Cav1.3-/- has a selective knockout for all Cav1.3 channels. Whereas the second modified mouse group Cav1.2-/- has a modified α1 subunit that inhibits the binding of agonists and antagonists from the channel. With the creation of these mice, creative studies can now selectively examine either isoform 1.2 or 1.3 depending on which pharmacological substances are utilized. Recent studies have now found that homologous knockouts of isoform 1.3 causes complete deafness, as well as sinoatrial node dysfunction. These results lend to the hypothesis that 1.3 specific calcium channels play a vital role in cochlear hair and sinoatrial node cell signaling transduction. Similarly, experiments utilizing Cav1.2-/- have revealed the importance in Ca2+ influx through Cav1.2 in regulating smooth muscle and cardiac contractility. This study also reiterates the importance of both isoforms in synaptic plasticity pertaining to memory, learning, and the storage of fear induced memories. Interestingly, when sensitivity to direct Ca2+ channel activators was inhibited in Cav1.2-/-, the efflux of glutamate from neurons in the ventral striatum was completely abolished, providing evidence for the importance of Cav1.2 in neurotransmission of glutamate. Again, I think this paper provides plausible evidence that L-type calcium channels may play an important role in synaptic plasticity within the RVLM. ~JI