This study investigates the role of Rad, a calcium channel inhibitor, in regulating cardiac L-type CaV1.2 channels during the fight-or-flight response. Researchers generated a Knockin mouse model (4SA-Rad) with four serine residues in Rad mutated to alanine, preventing phosphorylation by protein kinase A (PKA). These mice exhibited reduced basal heart rate, increased pauses, diminished contractility, and a near-complete loss of β-adrenergic response, highlighting the critical role of Rad phosphorylation in cardiac function.
Mice with the 4SA-Rad mutation displayed impaired β-adrenergic augmentation of calcium influx, leading to reduced heart rate and contractility. The study underscores the importance of Rad phosphorylation in modulating cardiac calcium channels and the fight-or-flight response.
4SA-Rad Knockin mouse model, engineered to express a Rad protein with four serine-to-alanine mutations, preventing PKA-mediated phosphorylation and thereby affecting CaV1.2 channel regulation.
Cardiac physiology, β-adrenergic signaling, Calcium channel regulation, Heart rate modulation, Fight-or-flight response
Knockin model, Point mutation, Serine-to-alanine substitution, PKA phosphorylation sites, Calcium channel modulation
From model design to experimental results
Tailor-made solutions adapted to scientific questions
Comprehensive dataset package
Generated with biopharma partners and in-house
Scientific follow-up and advice along the project
Collaborative approach for problem solving and development of innovative models
Breeding facilities in US and Europe
Certified health status from professional breeders
