Grant: Doctoral: Vanier Canada Graduate Scholarships

Supervisor: Dr. Peter Backx, York University Transient outward potassium channels (Ito) are vital in healthy heart function as they help regulate the timing and strength of heart contractions by directly affecting other transporters in muscle cells (i.e. cardiomyocytes) that control calcium. Importantly, the ability of Ito to perform these tasks varies between different heart regions, and my recent studies have demonstrated that the abundance of Ito is inversely related to the heart's electrical activation sequence. These findings suggest that Ito coordinates the timing of contractions to optimize the heart's pumping ability and efficiency. In support, Ito changes occur in many heart diseases involving dysregulated contractions, including atrial fibrillation, hypertension and heart failure, which commonly lead to cardiac-related death and disability. Interestingly, my most recent work reveals that Ito channels localize in distinct cardiomyocyte regions, alongside the transporters involved in calcium regulation, including sodium-calcium exchangers, calcium channels and sodium channels. These novel observations provide insights into how Ito controls the heart's pumping ability, and I now aim to uncover the interactions between Ito and these transporters that impact pumping efficiency. Thus, I have developed innovative strategies for understanding these mechanistic details, including the combined use of complimentary experimental and computational approaches, studies of Ito in healthy versus diseased hearts and the use of multiple species to assess the evolutionary role of Ito. My central hypothesis is that the regional variations in Ito abundance impact pumping efficiency and depend on interactions with the co-localized transporters described above. These studies will reveal the fundamental mechanisms underlying synchronized contractions in normal heart states and may provide insight for therapeutic avenues to treat major heart-related conditions when desynchronized.