The Role of Syntaxin-1A on Excitation-Contraction Coupling in the Adult Male and Female Mouse Heart

The SNARE protein, syntaxin-1A (STX1A) is expressed in the adult rodent heart, yet its role is not fully established. This thesis explored STX1As role in cardiac excitation-contraction (EC) coupling in male and female mouse hearts. Heart-specific homozygous and heterozygous STX1A knockouts were achieved via a tamoxifen-inducible Cre-Lox system. Echocardiography revealed significant systolic dysfunction post-STX1A knockout (week 0), with recovery beginning at week 1 and an absence of sex differences in cardiac function. Transient thickening of the posterior wall (week 1) and delayed contractions (week 0-3) were seen. No genetic compensation of STX2, 3, or 4 was seen, however, EC coupling genes, Cav1.2, RyR2, and SERCA2a, declined at week 0 and recovered at week 3, aligning with the phenotype recovery. Control Cre+ mice remained unchanged, suggesting the transient systolic dysfunction stems from compromised transcription of Ca2+ handling genes. Therefore, STX1A may facilitate normal EC coupling gene expression in adult mouse hearts.