Evaluating the impact of Cav1.2 mutations on neuronal function

Abstract

Timothy Syndrome (TS) is a multisystem disorder characterized by severe cardiac and neurological deficits including autism spectrum disorder (ASD). The cause of TS is a single point mutation in the CaV1.2 L-type Ca2+ channel (LTCC), and this mutation has been shown to disrupt channel regulation. The original TS mutation, G406R, imparts impaired voltage dependent inactivation, calcium dependent inactivation and voltage dependent activation, leading to this excess Ca2+ entry. Since the discovery of G406R, the number of known mutations in CaV1.2 has grown considerably, and biophysical studies have demonstrated varying effects of each mutation on the regulation of CaV1.2.