Theses and Dissertations
Advisor
Johnson, Christopher
Committee Member
Emerson, Joseph
Committee Member
Fitzkee, Nicholas
Date of Degree
8-7-2025
Original embargo terms
Embargo 2 years
Document Type
Graduate Thesis - Open Access
Major
Chemistry
Degree Name
Master of Science (M.S.)
College
College of Arts and Sciences
Department
Department of Chemistry
Abstract
Ion channels in the heart generate electrical currents that initiate contraction through changes in intracellular calcium concentration [Ca²⁺]. The ryanodine receptor type 2 (RyR2) mediates Ca²⁺ release from the sarcoplasmic reticulum (SR), and its dysregulation can lead to arrhythmias. Quantifying SR Ca²⁺ release events, such as sparks and waves, reveals mechanisms of RyR2 activity. This study used isolated, permeabilized mouse cardiomyocytes and leveraged mavacamten and SparkMaster 2 to assess RyR2 function under varying free [Ca²⁺] conditions. Kavalactones, bioactive compounds from Piper methysticum, were evaluated for their effects on SR Ca²⁺ release. A synthetic mixture was tested under physiological and pathological conditions, including calmodulin presence, RyR2 hyperphosphorylation by Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), and ATP depletion. Findings show that kavalactones modulate RyR2-mediated Ca²⁺ dynamics, affecting both normal and disease-mimicking states. These results offer insight into potential regulatory roles of natural products on cardiac calcium signaling and RyR2 function, relevant to cardiac health and therapeutic exploration.
Sponsorship (Optional)
N/A
Recommended Citation
Akter, Mahmuda, "The effect of synthetics kavalactones on sarcoplasmic reticulum Ca²⁺ release in healthy and molecular models of diseased cardiomyocytes." (2025). Theses and Dissertations. 6607.
https://scholarsjunction.msstate.edu/td/6607
