Sex, Age, and Regional Differences in L-Type Calcium Current Are Important Determinants of Arrhythmia Phenotype in Rabbit Hearts With Drug-Induced Long QT Type 2

In congenital and acquired long QT type 2, women are more vulnerable than men to Torsade de Pointes. In prepubertal rabbits (and children), the arrhythmia phenotype is reversed; however, females still have longer action potential durations than males. Thus, sex differences in K channels and action potential durations alone cannot account for sex-dependent arrhythmia phenotypes. The L-type calcium current (ICa,L) is another determinant of action potential duration, Ca overload, early afterdepolarizations (EADs), and Torsade de Pointes. Therefore, sex, age, and regional differences in ICa,L density and in EAD susceptibility were analyzed in epicardial left ventricular myocytes isolated from the apex and base of prepubertal and adult rabbit hearts. In prepubertal rabbits, peak ICa,L at the base was 22% higher in males than females (6.4±0.5 versus 5.0±0.2 pA/pF; P