Grant: Doctoral Research Award: Canada Graduate Scholarships

Transient outward potassium channels (Ito) are vital in healthy and diseased heart function. These channels help regulate the timing and strength of the heart's contraction 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 amount of Ito is inversely related to the heart's electrical activation sequence. These findings suggest that Ito helps coordinates the timing of contractions to optimize the heart's pumping efficiency. In support, changes in Ito occur in many heart diseases that present with 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 regions of cardiomyocytes, 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 more deeply, and I now aim to uncover the interactions of Ito with these transporters that impact pumping efficiency. As such, I have developed innovative strategies for understanding these mechanistic details. Included are the combined use of complimentary experimental and computational approaches, with assessments of Ito in healthy versus diseased hearts using animal models. I hypothesize that the regional variations in Ito impact pumping efficiency and depend on interactions with the co-localized transporters described above. These assessments will reveal the fundamental mechanisms underlying synchronized contractions in normal heart states and may provide additional therapeutic avenues to treat major heart conditions when desynchronized.