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O. HRYSHCHENKO, S. HUKE, F. BAUDENBACHER, J.D. POTTER, B.C. KNOLLMANN (2020) 'Ca2+ SENSITIZING TROPONIN T MUTATIONS LINKED TO HYPERTROPHIC CARDIOMYOPATHY INCREASE APPARENT CYTOSOLIC Ca2+ BINDING' in O.A. Krishtal, E.A. Lukyanetz (Eds.), ESSAYS ON NEUROPHYSIOLOGY BY PLATON KOSTYUK AND HIS STUDENTS, AKADEMPERIODYKA, pp. 217-222

Ca2+ SENSITIZING TROPONIN T MUTATIONS LINKED TO HYPERTROPHIC CARDIOMYOPATHY INCREASE APPARENT CYTOSOLIC Ca2+ BINDING

O. HRYSHCHENKO1, S. HUKE2, F. BAUDENBACHER3, J.D. POTTER4, B.C. KNOLLMANN2

  1. Bogomoletz Institute of physiology NAS of Ukraine, Kyiv, Ukraine
  2. Vanderbilt University, Division of Clin Pharmacology, Nashville, TN, USA
  3. Vanderbilt University, Institute for Integrative Biosystems Research and Education (VIIBRE), Nashville, TN, USA
  4. University of Miami, Molecular and Cellular Pharmacology, Miami, FL, USA
DOI: https://doi.org/10.15407/biph.books.EssNeur.217


Abstract

In intact contracting myocytes, the cytosolic free Ca²⁺ concentration ([Ca²⁺]free) varies dynamically and is determined by the sarcolemmal and trans-sarcoplasmic reticulum Ca²⁺ fluxes, the binding kinetics to Ca²⁺ ligands in the cytosol (Ca²⁺ buffering), and, to a lesser extent, by mitochondrial Ca²⁺ fluxes (Shannon and Bers, 2004; Bers, 2001). Major Ca²⁺ binding ligands are the myofilament protein Troponin C (TnC; about 50% of fast Ca²⁺ binding during a typical heartbeat), the sarcoplasmic reticulum (SR) Ca²⁺ ATPase (SERCA), and binding sites along the sarcolemmal membrane which remain to be identified (Bers, 2001; Fabiato, 1983). Additional Ca²⁺ is bound by slow Ca²⁺ buffering sites (Shannon and Bers, 2004). However, these high-affinity Ca²⁺/Mg²⁺ binding sites are largely saturated with Mg²⁺ during diastole (Robertson et al., 1981). Other high-capacity, low-affinity buffers (e.g., ATP, creatine phosphate) in aggregate also significantly contribute to Ca²⁺ buffering (Bers, 2001).

Keywords: calcium buffering, troponin T mutations, hypertrophic cardiomyopathy, excitation-contraction coupling, ventricular arrhythmias, sarcoplasmic reticulum, sodium-calcium exchanger, myofilament Ca2+ sensitivity, cytosolic Ca2+ transients, cardiac electrophysiology

Full text: (PDF, in English)

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