Abstract
Alteration in how the cardiomyocyte manages intracellular calcium is not only important acutely in alteration of the cardiac action potential leading to potentially arrhythmogenic changes within the myocardium, but long-term, global changes in intracellular calcium have been linked to hypertrophy and heart failure [1–3]. Recent work implicates the NFATc3 transcription factor as a key player that translates these changes in intracellular calcium into changes in gene expression, ion current remodeling, and ultimately reshaping of the cardiac action potential via reduction in repolarizing Kv currents. As early as 48 h post MI, this reduction in repolarizing K+ currents leads to an increase in action potential duration (APD), QT interval prolongation, and thereby increases the probability for developing potentially life-threatening arrhythmias [4]. Under more chronic conditions, this reshaping of the cardiac action potential leads to a global increase in intracellular calcium via an increase in the open probability of the LTCC due to prolongation of phase 2 of the cardiac action potential and ultimately activation of genes leading to hypertrophy and HF. Data suggest that the initiating event for these changes in intracellular calcium is the increase in β-AR stimulation seen with the catecholamine surge during acute MI or decompensated HF [5, 6].
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Santana, L.F. (2013). Heart Failure: The Final Frontier for Biophysics in Cardiovascular Medicine?. In: Solaro, R., Tardiff, J. (eds) Biophysics of the Failing Heart. Biological and Medical Physics, Biomedical Engineering. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7678-8_8
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