SF domain mutation enhances inactivation of TS-associated Ca _V 1.2 mutant channel. (A) Top: Wild-type human Ca_V1.2 channel exhibits robust CDI and VDI. Black trace, Ba²⁺ current; red trace, Ca²⁺ current. Bottom: Population data show baseline inactivation of Ca_V1.2 measured as r₃₀₀, the fraction of peak current remaining following 300 ms, with either Ca²⁺ (red) or Ba²⁺ (black) as the charge carrier. Each symbol, mean ± SEM. n = 5 cells. (B) Ca_V1.2 G406R mutant linked to TS shows reduced VDI and CDI. Format as in panel A. n = 6 cells. (C) Introducing the DIV W[+2]A mutation on TS-linked CaV1.2 G406R background enhances VDI. This finding suggests that increasing the conformational flexibility of DIV SF may be a potential approach to reverse TS pathophysiology. n = 6 cells.