Commentary: Peptide-Based Targeting of the L-Type Calcium Channel Corrects the Loss-of-Function Phenotype of Two Novel Mutations of the CACNA1 Gene Associated With Brugada Syndrome

Michelle M. Monasky, Carola Rutigliani, Emanuele Micaglio, Carlo Pappone
2021 Frontiers in Physiology  
We read with great interest a recently published article by Di Mauro et al. (2020) describing for the first time the use of a mimetic peptide (R7W-MP) to restore impaired forward trafficking and reduced half-life of L-type calcium channels (LTCC) caused by mutations in the CACNA1C gene, restoring channel function in vitro. The two novel mutations in the CACNA1C gene (Cavα1.2 T320M and Cavα1.2 Q428E) were found in patients with Brugada syndrome (BrS), one asymptomatic (T320M), and one with a
more » ... and one with a history of cardiac arrest, ICD placement, two episodes of self-terminating polymorphic ventricular tachycardia, and runs of atrial fibrillation (Q428E). The mutations in the CACNA1C gene, encoding for the pore-forming unit (Cavα1.2), studied in HEK293 cells, exhibited reduced protein trafficking to, and half-life in, the membrane, resulting in reduced calcium current.
doi:10.3389/fphys.2021.682567 pmid:34177625 pmcid:PMC8220137 fatcat:kogqlgbzbveu7fbqwnoxumpzwa