scholarly journals Optogenetic actuation in ChR2-transduced fibroblasts alter excitation-contraction coupling and mechano-electric feedback in coupled cardiomyocytes: a computational modeling study

2021 ◽  
Vol 18 (6) ◽  
pp. 8354-8373
Author(s):  
Heqing Zhan ◽  
◽  
Zefeng Wang ◽  
Jialun Lin ◽  
Yuanbo Yu ◽  
...  
Keyword(s):  
Cardiac Fibroblasts ◽  
Inward Rectification ◽  
Muscle Twitch ◽  
Combined Model ◽  
Electrical Method ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Reverse Mode ◽  
Light Duration ◽  
Prolonged Duration

<abstract> <p>With the help of the conventional electrical method and the growing optogenetic technology, cardiac fibroblasts (Fbs) have been verified to couple electrically with working myocytes and bring electrophysiological remodeling changes in them. The intrinsic properties of cardiac functional autoregulation represented by excitation-contraction coupling (ECC) and mechano-electric feedback (MEF) have also been extensively studied. However, the roles of optogenetic stimulation on the characteristics of ECC and MEF in cardiomyocytes (CMs) coupled with Fbs have been barely investigated. In this study, we proposed a combined model composed of three modules to explore these influences. Simulation results showed that (1) during ECC, an increased light duration (LD) strengthened the inflow of ChR2 current and prolonged action potential duration (APD), and extended durations of twitch and internal sarcomere deformation through the decreased dissociation of calcium with troponin C (CaTnC) complexes and the prolonged duration of Xb attachment-detachment; (2) during MEF, an increased LD was followed by a longer muscle twitch and deformation, and led to APD prolongation through the inward ChR2 current and its inward rectification kinetics, which far outweighed the effects of the delaying dissociation of CaTnC complexes and the prolonged reverse mode of Na<sup>+</sup>-Ca<sup>2+</sup> exchange on AP shortening; (3) due to the ChR2 current's rectification feature, enhancing the light irradiance (LI) brought slight variations in peak or valley values of electrophysiological and mechanical parameters while did not change durations of AP and twitch and muscle deformation in both ECC and MEF. In conclusion, the inward ChR2 current and its inward rectification feature were found to affect significantly the durations of AP and twitch in both ECC and MEF. The roles of optogenetic actuation on both ECC and MEF should be considered in future cardiac computational optogenetics at the tissue and organ scale.</p> </abstract>

scholarly journals Effects of mitochondrial uncoupling on Ca2+ signaling during excitation-contraction coupling in atrial myocytes

2013 ◽  
Vol 304 (7) ◽  
pp. H983-H993 ◽  
Author(s):  
Aleksey V. Zima ◽  
Malikarjuna R. Pabbidi ◽  
Stephen L. Lipsius ◽  
Lothar A. Blatter
Keyword(s):  
Ion Homeostasis ◽  
Inhibitory Effect ◽  
Partial Recovery ◽  
Atrial Myocytes ◽  
Mitochondrial Uncoupling ◽  
Release Channel ◽  
Excitation Contraction Coupling ◽  
Atp Production ◽  
Contraction Coupling ◽  
Reverse Mode

Mitochondria play an important role in intracellular Ca2+ concentration ([Ca2+]i) regulation in the heart. We studied sarcoplasmic reticulum (SR) Ca2+ release in cat atrial myocytes during depolarization of mitochondrial membrane potential (ΔΨm) induced by the protonophore FCCP. FCCP caused an initial decrease of action potential-induced Ca2+ transient amplitude and frequency of spontaneous Ca2+ waves followed by partial recovery despite partially depleted SR Ca2+ stores. In the presence of oligomycin, FCCP only exerted a stimulatory effect on Ca2+ transients and Ca2+ wave frequency, suggesting that the inhibitory effect of FCCP was mediated by ATP consumption through reverse-mode operation of mitochondrial F1F0-ATPase. ΔΨm depolarization was accompanied by cytosolic acidification, increases of diastolic [Ca2+]i, intracellular Na+ concentration ([Na+]i), and intracellular Mg2+ concentration ([Mg2+]i), and a decrease of intracellular ATP concentration ([ATP]i); however, glycolytic ATP production partially compensated for the exhaustion of mitochondrial ATP supplies. In conclusion, the initial inhibition of Ca2+ transients and waves resulted from suppression of ryanodine receptor SR Ca2+ release channel activity by a decrease in [ATP], an increase of [Mg2+]i, and cytoplasmic acidification. The later stimulation resulted from reduced mitochondrial Ca2+ buffering and cytosolic Na+ and Ca2+ accumulation, leading to enhanced Ca2+-induced Ca2+ release and spontaneous Ca2+ release in the form of Ca2+ waves. ΔΨm depolarization and the ensuing consequences of mitochondrial uncoupling observed here (intracellular acidification, decrease of [ATP]i, increase of [Na+]i and [Mg2+]i, and Ca2+ overload) are hallmarks of ischemia. These findings may therefore provide insight into the consequences of mitochondrial uncoupling for ion homeostasis, SR Ca2+ release, and excitation-contraction coupling in ischemia at the cellular and subcellular level.

Role of Reverse-Mode Na+-Ca2+Exchange in Excitation-Contraction Coupling in the Heart

1991 ◽  
Vol 639 (1 Sodium-Calciu) ◽  
pp. 386-397 ◽  
Author(s):  
PAUL C. LEVESQUE ◽  
NORMAND LEBLANC ◽  
JOSEPH R. HUME
Keyword(s):  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Reverse Mode

scholarly journals High [Na+]i in cardiomyocytes from rainbow trout

2007 ◽  
Vol 293 (2) ◽  
pp. R861-R866 ◽  
Author(s):  
Rikke Birkedal ◽  
Holly A. Shiels
Keyword(s):  
Rainbow Trout ◽  
Ventricular Myocytes ◽  
Resting Cells ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Contraction Frequency ◽  
Reverse Mode ◽  
Whole Cell Patch Clamp ◽  
Ventricular Cells

Intracellular Na+-concentration, [Na+]i modulates excitation-contraction coupling of cardiac myocytes via the Na+/Ca2+ exchanger (NCX). In cardiomyocytes from rainbow trout ( Oncorhyncus mykiss), whole cell patch-clamp studies have shown that Ca2+ influx via reverse-mode NCX contributes significantly to contraction when [Na+]i is 16 mM but not 10 mM. However, physiological [Na+]i has never been measured. We recorded [Na+]i using the fluorescent indicator sodium-binding benzofuran isophthalate in freshly isolated atrial and ventricular myocytes from rainbow trout. We examined [Na+]i at rest and during increases in contraction frequency across three temperatures that span those trout experience in nature (7, 14, and 21°C). Surprisingly, we found that [Na+]i was not different between atrial and ventricular cells. Furthermore, acute temperature changes did not affect [Na+]i in resting cells. Thus, we report a resting in vivo [Na+]i of 13.4 mM for rainbow trout cardiomyocytes. [Na+]i increased from rest with increases in contraction frequency by 3.2, 4.7, and 6.5% at 0.2, 0.5, and 0.8 Hz, respectively. This corresponds to an increase of 0.4, 0.6, and 0.9 mM at 0.2, 0.5, and 0.8 Hz, respectively. Acute temperature change did not significantly affect the contraction-induced increase in [Na+]i. Our results provide the first measurement of [Na+]i in rainbow trout cardiomyocytes. This surprisingly high [Na+]i is likely to result in physiologically significant Ca2+ influx via reverse-mode NCX during excitation-contraction coupling. We calculate that this Ca2+-source will decrease with the action potential duration as temperature and contraction frequency increases.

scholarly journals Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yankun Lyu ◽  
Vipin K. Verma ◽  
Younjee Lee ◽  
Iosif Taleb ◽  
Rachit Badolia ◽  
...  
Keyword(s):  
Heart Function ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Excitation Contraction Coupling ◽  
Transverse Tubular System ◽  
Contraction Coupling ◽  
Senescent Phenotype ◽  
Cellular Microstructure ◽  
T System

AbstractIt is well established that the aging heart progressively remodels towards a senescent phenotype, but alterations of cellular microstructure and their differences to chronic heart failure (HF) associated remodeling remain ill-defined. Here, we show that the transverse tubular system (t-system) and proteins underlying excitation-contraction coupling in cardiomyocytes are characteristically remodeled with age. We shed light on mechanisms of this remodeling and identified similarities and differences to chronic HF. Using left ventricular myocardium from donors and HF patients with ages between 19 and 75 years, we established a library of 3D reconstructions of the t-system as well as ryanodine receptor (RyR) and junctophilin 2 (JPH2) clusters. Aging was characterized by t-system alterations and sarcolemmal dissociation of RyR clusters. This remodeling was less pronounced than in HF and accompanied by major alterations of JPH2 arrangement. Our study indicates that targeting sarcolemmal association of JPH2 might ameliorate age-associated deficiencies of heart function.

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