scholarly journals New Insights in Cardiac Calcium Handling and Excitation-Contraction Coupling

2017 ◽  
pp. 373-385 ◽  
Author(s):  
Jessica Gambardella ◽  
Bruno Trimarco ◽  
Guido Iaccarino ◽  
Gaetano Santulli
Keyword(s):  
Calcium Handling ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling

Abstract P498: Polycystin-1 Regulates Excitation-contraction Coupling In Atrial Cardiomyocytes

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Troy Hendrickson ◽  
William Perez ◽  
Vincent Provasek ◽  
Francisco J Altamirano
Keyword(s):  
Electrical Stimulation ◽  
Action Potentials ◽  
Primary Cilia ◽  
Calcium Influx ◽  
Calcium Transient ◽  
Calcium Handling ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Atrial Cardiomyocytes ◽  
Atrial Excitation

Patients with Autosomal Dominant Polycystic Kidney disease (ADPKD) have multiple cardiovascular manifestations, including increased susceptibility to arrhythmias. Mutations in polycystin-1 (PC1) encoding gene accounts for 85% cases of ADPKD, whereas mutations in polycystin-2 (PC2) only accounts for 15%. In kidney cells, PC1 interacts with PC2 to form a protein complex at the primary cilia to regulate calcium influx via PC2. However, cardiomyocytes are non-ciliated cells and the role of both PC1 and PC2 in atrial cardiomyocytes remains unknown. We have previously demonstrated that PC1 regulates action potentials and calcium handling to fine-tune ventricular cardiomyocyte contraction. Here, we hypothesize that PC1 regulates action potentials and calcium handling in atrial cardiomyocytes independent of PC2 actions. To test this hypothesis, we differentiated human induced pluripotent stem cells (iPSC) into atrial cardiomyocytes (iPSC-aCM) using previously published protocols. To determine the contribution of PC1/PC2 in atrial excitation-contraction coupling, protein expression was knocked down utilizing specific siRNA constructs, for each protein, or a universal control siRNA transfected using lipofectamine RNAiMAX. We measured action potentials using the potentiometric dye FluoVolt and intracellular calcium with Fura-2 AM or Fluo-4. Changes in fluorescence were monitored using a multiwavelength IonOptix system. iPSC-aCM were paced at 2 Hz to synchronize the beating pattern using field electrical stimulation. Our data shows that PC1 ablation significantly decreased action potential duration at 50% and 80% of repolarization, by 24% and 23%, respectively. Moreover, we observed that PC1 knockdown significantly reduced calcium transient amplitude elicited by field electrical stimulation without changes in calcium transient decay. Interestingly, PC2 knockdown did not modify calcium transients in atrial cardiomyocytes (iPSC-aCM). Our data suggest that PC1 regulates atrial excitation-contraction coupling independent of PC2 actions. This study warrants further investigation into atrial dysfunction in ADPKD patients with PC1 mutations.

scholarly journals Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback

2014 ◽  
Vol 136 (2) ◽  
Author(s):  
Emily R. Pfeiffer ◽  
Jared R. Tangney ◽  
Jeffrey H. Omens ◽  
Andrew D. McCulloch
Keyword(s):  
Heart Failure ◽  
Intracellular Calcium ◽  
Model Systems ◽  
Calcium Handling ◽  
Scale Model ◽  
Mechanoelectric Feedback ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Cardiac Wall ◽  
Increased Risk

Cardiac mechanical contraction is triggered by electrical activation via an intracellular calcium-dependent process known as excitation–contraction coupling. Dysregulation of cardiac myocyte intracellular calcium handling is a common feature of heart failure. At the organ scale, electrical dyssynchrony leads to mechanical alterations and exacerbates pump dysfunction in heart failure. A reverse coupling between cardiac mechanics and electrophysiology is also well established. It is commonly referred as cardiac mechanoelectric feedback and thought to be an important contributor to the increased risk of arrhythmia during pathological conditions that alter regional cardiac wall mechanics, including heart failure. At the cellular scale, most investigations of myocyte mechanoelectric feedback have focused on the roles of stretch-activated ion channels, though mechanisms that are independent of ionic currents have also been described. Here we review excitation–contraction coupling and mechanoelectric feedback at the cellular and organ scales, and we identify the need for new multicellular tissue-scale model systems and experiments that can help us to obtain a better understanding of how interactions between electrophysiological and mechanical processes at the cell scale affect ventricular electromechanical interactions at the organ scale in the normal and diseased heart.

scholarly journals Excitation Contraction Coupling in Hypertrophy and Failing Heart Cells

2021 ◽  
Vol 271 ◽  
pp. 03008
Author(s):  
Yiqiu Zhou
Keyword(s):  
Heart Failure ◽  
Calcium Release ◽  
Heart Diseases ◽  
Calcium Handling ◽  
Heart Cells ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Failing Heart ◽  
Failure Models ◽  
And Function

The contraction of the heart is dependent on a process named the excitation-contraction coupling (E-C coupling). In hypertrophy and failing heart models, the expression, phosphorylation and function of key calcium handling proteins involved in E-C coupling are altered. It’s important to figure out the relationship changes between calcium channel activity and calcium release from sarcoplasmic reticulum (SR). This review will therefore focus on novel components of E-C coupling dysfunction in hypertrophy and failing heart, such as L-type Ca2+ channel (LCC), ryanodine receptor type-2 channel (RyR2) and SR Ca ATPase (SERCA), and how these molecular modifications altered excitation-contraction coupling. A lot of literature was well read and sorted. Recent findings in E-C coupling during hypertrophy and heart failure were focused on. Most importantly, the electrophysiological and signal pathway data was carefully analyzed. This review summarizes key principles and highlights novel aspects of E-C coupling changes during hypertrophy and heart failure models. Although LCC activity changed little, the loss of notch in action potential, reduced Ca2+ transient amplitude and desynchronized Ca2+ sparks resulted in a decreased contraction strength in hypertrophy and heart failure models. What’s more, L-type Ca2+ current becomes ineffective in triggering RyR2 Ca2+ release from SR and the SR uptake is reduced in some models. It has great meanings in understanding the E-C coupling changes during different heart diseases. Theses novel changes suggest potential therapeutic approaches for certain types of hypertrophy and heart failure.

scholarly journals The effect of lead on the calcium-handling capacity of rat heart mitochondria

1976 ◽  
Vol 158 (2) ◽  
pp. 289-294 ◽  
Author(s):  
D R Parr ◽  
E J Harris
Keyword(s):  
Rat Heart ◽  
Heart Tissue ◽  
Calcium Handling ◽  
Primary Effect ◽  
Heart Mitochondria ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Low Concentrations ◽  
Rat Heart Mitochondria

1. Very low concentrations of Pb2+ decrease the capacity of rat heart mitochondria, oxidizing pyruvate plus malate, to remove Ca2+ from the medium. 2. The primary effect is on the rate of Ca2+ sequestration; this is reflected in the overall extent of Ca2+ removal. 3. Pb2+ has at least two separate actions. Below about 0.5 nmol/mg of protein, it acts solely by competing with Ca2+ (Ki = 0.4 muM); above this concentration it also inhibits the production or use of respiratory energy, so that at 1 nmol of Pb2+/mg of protein, Ca2+ removal is almost completely abolished. 4. Pb2+ inhibits coupled and uncoupled respiratory O2 use by mitochondria oxidizing pyruvate plus malate, but at higher concentrations than those that affect Ca2+ removal; similar concentrations of Pb2+ inhibit pyruvate uptake, but not malate uptake, by the mitochondria. 5. Mg2+ only decreases Ca2+ removal by competition, and is a far-less effective competitor than Pb2+ (Ki = 0.15 mM). It is possible that the primary cause of the second effect of Pb2+ is displacement of membrane Mg2+. 6. The consequences of these results are discussed in terms of the possible involvement of heart mitochondria in excitation-contraction coupling, and the Pb2+ levels that might occur in heart tissue in vivo.

scholarly journals Studying dyadic structure–function relationships: a review of current modeling approaches and new insights into Ca2+ (mis)handling

2017 ◽  
Vol 11 ◽  
pp. 117954681769860 ◽  
Author(s):  
Mary M Maleckar ◽  
Andrew G Edwards ◽  
William E Louch ◽  
Glenn T Lines
Keyword(s):  
Heart Disease ◽  
Sarcoplasmic Reticulum ◽  
Structure Function ◽  
Cardiac Myocytes ◽  
Calcium Release ◽  
Calcium Handling ◽  
Protein Distribution ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Calcium Dependent

Excitation–contraction coupling in cardiac myocytes requires calcium influx through L-type calcium channels in the sarcolemma, which gates calcium release through sarcoplasmic reticulum ryanodine receptors in a process known as calcium-induced calcium release, producing a myoplasmic calcium transient and enabling cardiomyocyte contraction. The spatio-temporal dynamics of calcium release, buffering, and reuptake into the sarcoplasmic reticulum play a central role in excitation–contraction coupling in both normal and diseased cardiac myocytes. However, further quantitative understanding of these cells’ calcium machinery and the study of mechanisms that underlie both normal cardiac function and calcium-dependent etiologies in heart disease requires accurate knowledge of cardiac ultrastructure, protein distribution and subcellular function. As current imaging techniques are limited in spatial resolution, limiting insight into changes in calcium handling, computational models of excitation–contraction coupling have been increasingly employed to probe these structure–function relationships. This review will focus on the development of structural models of cardiac calcium dynamics at the subcellular level, orienting the reader broadly towards the development of models of subcellular calcium handling in cardiomyocytes. Specific focus will be given to progress in recent years in terms of multi-scale modeling employing resolved spatial models of subcellular calcium machinery. A review of the state-of-the-art will be followed by a review of emergent insights into calcium-dependent etiologies in heart disease and, finally, we will offer a perspective on future directions for related computational modeling and simulation efforts.

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