CBAC Seminar Series Videos
Sex, Calcium and Arrhythmias


Sex, Calcium and Arrhythmias


Link to Full Video

Stream Seminar Video


Spring 3-31-2014

Document Type

Seminar Series


Women have a longer baseline QTc than men, and are at higher risk (60-75%) for long QT syndrome (LQTS) than men. LQTS is characterized by sudden syncopal attacks, seizures, and sudden death. LQTS is associated with a form of polymorphic ventricular tachycardia, called Torsade de Pointes (TdP) which often leads to sudden death and remains a major health problem. TdP caused by the suppression of the fast component of the delayed rectifying K+ current, IKr results in repolarization delay and QT prolongation, called Long QT type 2 (LQT2). Sex differences in the propensity to LQT2 have been attributed to a reduced ‘repolarization reserve’ in females and is observed in other mammalian hearts (rabbits, dogs and guinea pigs). Recent studies from our group has discovered that in rabbit hearts, estrogen (0.3-1nM) upregulates voltage-gated L-type Ca2+ channels and Na/Ca exchanger (NCX) to increase their currents, ICa,L and INCX selectively at the base of the heart. Estrogen acts via a genomic mechanism (in 24-48 hrs) to increase levels of message, protein and current densities. Repolarization delay prolongs the action potential, changes the balance of Ca2+ influx vs. efflux leading to sarcoplasmic reticulum (SR) Ca2+ overload. In minutes, SR overload produces cell-synchronous systolic secondary Ca2+ elevations (SSCEs) in local islands of epicardium. SSCEs precede voltage depolarization during the AP-plateau and cause the re-activation of L-type Ca2+ channels, ectopic beats and TdP. Parallels between rabbit model of drug-induced LQT2 and human tissues will be discussed.


Professor of Cardiology, and of Cell Biology, University of Pittsburgh School of Medicine

Research/Clinical Interests


Sex, Calcium and Arrhythmias