In 2014, it was reported in SLEEP that CaV2.3-deficient mice exhibited reduced wake duration and increased slow wave sleep.1 These results differ from those received in another mouse line proven to lack CaV2.3 protein.2
In 2013 it was published in Somnologie that CaV2.3-deficient mice display reduced total sleep time and an impairment of SWS generation as well as significantly reduced delta power.3 One explanation of these contradictions may be based on the mouse lines used in both studies. The two CaV2.3-deficient mouse lines differ by the site of initiation of cacna1e gene inactivation. The ablation of CaV2.3 by deletion of exon 2 causes an impairment of protein expression of CaV2.3, which was proven by Western blotting using antibodies directed against domain I or domain IV of CaV2.3.2 However, in the mouse line used by Siwek and coworkers, the cacna1e gene was targeted at a site more downstream of domain I by replacing the S4-S6 regions of domain II with a neomycin/URA3 selection cassette, which may leave behind a truncated part of the central ion conducting subunit.4
Truncated but functional voltage-gated Ca2+ channels have been identified for a related gene, the central subunit of neuronal L-type voltage-gated Ca2+ channels.5 Similarly, a truncated cacna1e gene may be predisposed to arrangement forming an active channel resembling an overexpression of CaV2.3. It cannot be excluded that a truncated CaV2.3 channel mainly containing domain I and part of domain II may still be expressed or may influence the activity of similar voltage-gated Ca2+ channels by association. This may explain the opposing results reported from both groups.
CITATION
Schneider T, Dibué-Adjei M. CaV2.3 E-/R-type voltage-gated calcium channels modulate sleep in mice. SLEEP 2015;38(3):499.
DISCLOSURE STATEMENT
This was not an industry supported study. The authors have indicated no financial conflicts of interest.
REFERENCES
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