New Insights in Cardiac Calcium Handling and Excitation-Contraction Coupling

Abstract

Excitation-contraction (EC) coupling denotes the conversion of electric stimulus in mechanic output in contractile cells. Several studies have demonstrated that calcium (Ca2+) plays a pivotal role in this process. Here we present a comprehensive and updated description of the main systems involved in cardiac Ca2+ handling that ensure a functional EC coupling and their pathological alterations, mainly related to heart failure.

Ryanodine Receptor Structure and Function in Health and Disease

“…The majority of the known post-translational modifications and modulatory protein binding sites are situated on the cytoplasmic shell and influence the cytoplasmic shell dynamics and therefore, indirectly, gating (Gambardella et al 2017). The shell dynamics could be influenced in several ways: The rigidity of the protomer assembly could be altered, as suggested with calstabins; the strength of interprotomer contacts could be modified, thereby influencing shell movement and gating; the shell movement could be directly constrained, which would either promote (e.g., DHPR) or prevent the outward motion necessary for pore opening (Bai et al 2016; des Georges et al 2016).…”

Crosstalk between Mitochondria and Cytoskeleton in Cardiac Cells

“…However, increased mitochondrial and cytosolic Ca 2+ may lead to various pathologies and diseases, such as IRI, hypoxia-reoxygenation, arrhythmias, hypertension, heart failure, and metabolic syndrome, etc. [179,[181][182][183][184]. This can be tightly associated with multiple Ca 2+ -modulated processes, such as: mitochondria/cell swelling, changes in the interactions between cytoskeleton, mitochondria, and SR, decline of ∆Ψm, diminished mitochondrial respiratory capacity and consequent decreased cellular ATP content (energy stress), altered mitochondrial dynamics (fission-fusion balance, Drp1 signaling), increased ROS (oxidative stress), and induction of apoptosis [179,183,185].…”

Role of Calcium Ions in Excitation-Contraction Coupling in Cardiomyocytes

“…Під час скорочення воно відразу змінюється приблизно до 10: 1 [10]. Буферизація кальцію забезпечує оптимальне видалення вільного Ca 2+ з цитозолю, щоб забезпечити потрібну кількість, доступну для скорочення в наступному ритмі [11].…”

“…Вони тісно пов'язані з родиною RyR, розділяючи з ними високу структурну гомологію [72]. IP 3 Rs експресуются у міоцитах передсердя з високою щільністю [11]. У клітинах шлуночків вони відсутні [73].…”