scholarly journals Role of Cytosolic Calcium Diffusion in Murine Cardiac Purkinje Cells

2016 ◽  
Vol 10s1 ◽  
pp. CMC.S39705
Author(s):  
Bijay Limbu ◽  
Kushal Shah ◽  
Seth H. Weinberg ◽  
Makarand Deo
Keyword(s):  
Purkinje Cells ◽  
Ventricular Myocytes ◽  
Ionic Current ◽  
Cytosolic Calcium ◽  
Diffusion Waves ◽  
Cardiac Purkinje Cells ◽  
Calcium Diffusion ◽  
Intracellular Ca ◽  
Diffusion Rates

Cardiac Purkinje cells (PCs) are morphologically and electrophysiologically different from ventricular myocytes and, importantly, exhibit distinct calcium (Ca2+) homeostasis. Recent studies suggest that PCs are more susceptible to action potential (AP) abnormalities than ventricular myocytes; however, the exact mechanisms are poorly understood. In this study, we utilized a detailed biophysical mathematical model of a murine PC to systematically examine the role of cytosolic Ca2+ diffusion in shaping the AP in PCs. A biphasic spatiotemporal Ca2+ diffusion process, as recorded experimentally, was implemented in the model. In this study, we investigated the role of cytosolic Ca2+ dynamics on AP and ionic current properties by varying the effective Ca2+ diffusion rate. It was observed that AP morphology, specifically the plateau, was affected due to changes in the intracellular Ca2+ dynamics. Elevated Ca2+ concentration in the sarcolemmal region activated inward sodium-Ca2+ exchanger (NCX) current, resulting in a prolongation of the AP plateau at faster diffusion rates. Artificially clamping the NCX current to control values completely reversed the alterations in the AP plateau, thus confirming the role of NCX in modifying the AP morphology. Our results demonstrate that cytosolic Ca2+ diffusion waves play a significant role in shaping APs of PCs and could provide mechanistic insights in the increased arrhythmogeneity of PCs.

Role of Cytosolic Calcium Diffusion and Sarcolemmal T-Type Calcium Current in Triggered Activity in Purkinje Cells: A Simulation Study

Heart Rhythm ◽  
2011 ◽  
Vol 8 (11) ◽  
pp. 1821
Author(s):  
M. Deo ◽  
S.V. Pandit ◽  
R. Vaidyanathan ◽  
R. OConnell ◽  
M. Milstein ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Simulation Study ◽  
Calcium Current ◽  
Cytosolic Calcium ◽  
Triggered Activity ◽  
Calcium Diffusion

scholarly journals Stretch-activated channel activation promotes early afterdepolarizations in rat ventricular myocytes under oxidative stress

2009 ◽  
Vol 296 (5) ◽  
pp. H1227-H1235 ◽  
Author(s):  
Yanggan Wang ◽  
Ronald W. Joyner ◽  
Mary B. Wagner ◽  
Jun Cheng ◽  
Dongwu Lai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ventricular Myocytes ◽  
Ionic Current ◽  
Reversal Potential ◽  
Mechanical Stretch ◽  
Early Afterdepolarizations ◽  
Rat Ventricular Myocytes ◽  
Intracellular Ca ◽  
And Oxidative Stress

Mechanical stretch and oxidative stress have been shown to prolong action potential duration (APD) and produce early afterdepolarizations (EADs). Here, we developed a simulation model to study the role of stretch-activated channel (SAC) currents in triggering EADs in ventricular myocytes under oxidative stress. We adapted our coupling clamp circuit so that a model ionic current representing the actual SAC current was injected into ventricular myocytes and added as a real-time current. This current was calculated as ISAC = GSAC * ( Vm − ESAC), where GSAC is the stretch-activated conductance, Vm is the membrane potential, and ESAC is the reversal potential. In rat ventricular myocytes, application of GSAC did not produce sustained automaticity or EADs, although turn-on of GSAC did produce some transient automaticity at high levels of GSAC. Exposure of myocytes to 100 μM H2O2 induced significant APD prolongation and increase in intracellular Ca2+ load and transient, but no EAD or sustained automaticity was generated in the absence of GSAC. However, the combination of GSAC and H2O2 consistently produced EADs at lower levels of GSAC (2.6 ± 0.4 nS, n = 14, P < 0.05). Pacing myocytes at a faster rate further prolonged APD and promoted the development of EADs. SAC activation plays an important role in facilitating the development of EADs in ventricular myocytes under acute oxidative stress. This mechanism may contribute to the increased propensity to lethal ventricular arrhythmias seen in cardiomyopathies, where the myocardium stretch and oxidative stress generally coexist.

scholarly journals The calcium stored in the sarcoplasmic reticulum acts as a safety mechanism in rainbow trout heart

2014 ◽  
Vol 307 (12) ◽  
pp. R1493-R1501 ◽  
Author(s):  
Caroline Cros ◽  
Laurent Sallé ◽  
Daniel E. Warren ◽  
Holly A. Shiels ◽  
Fabien Brette
Keyword(s):  
Rainbow Trout ◽  
Sarcoplasmic Reticulum ◽  
Ventricular Myocytes ◽  
Adrenergic Stimulation ◽  
Relative Contribution ◽  
Safety Mechanism ◽  
Rapid Changes ◽  
Intracellular Ca ◽  
As Stress

Cardiomyocyte contraction depends on rapid changes in intracellular Ca2+. In mammals, Ca2+ influx as L-type Ca2+ current ( ICa) triggers the release of Ca2+ from sarcoplasmic reticulum (SR) and Ca2+-induced Ca2+ release (CICR) is critical for excitation-contraction coupling. In fish, the relative contribution of external and internal Ca2+ is unclear. Here, we characterized the role of ICa to trigger SR Ca2+ release in rainbow trout ventricular myocytes using ICa regulation by Ca2+ as an index of CICR. ICa was recorded with a slow (EGTA) or fast (BAPTA) Ca2+ chelator in control and isoproterenol conditions. In the absence of β-adrenergic stimulation, the rate of ICa inactivation was not significantly different in EGTA and BAPTA (27.1 ± 1.8 vs. 30.3 ± 2.4 ms), whereas with isoproterenol (1 μM), inactivation was significantly faster with EGTA (11.6 ± 1.7 vs. 27.3 ± 1.6 ms). When barium was the charge carrier, inactivation was significantly slower in both conditions (61.9 ± 6.1 vs. 68.0 ± 8.7 ms, control, isoproterenol). Quantification revealed that without isoproterenol, only 39% of ICa inactivation was due to Ca2+, while with isoproterenol, inactivation was Ca2+-dependent (∼65%) and highly reliant on SR Ca2+ (∼46%). Thus, SR Ca2+ is not released in basal conditions, and ICa is the main trigger of contraction, whereas during a stress response, SR Ca2+ is an important source of cytosolic Ca2+. This was not attributed to differences in SR Ca2+ load because caffeine-induced transients were not different in both conditions. Therefore, Ca2+ stored in SR of trout cardiomyocytes may act as a safety mechanism, allowing greater contraction when higher contractility is required, such as stress or exercise.

Properties of potassium currents in Purkinje cells of failing human hearts

2002 ◽  
Vol 283 (6) ◽  
pp. H2495-H2503 ◽  
Author(s):  
Wei Han ◽  
Liming Zhang ◽  
Gernot Schram ◽  
Stanley Nattel
Keyword(s):  
Purkinje Cells ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Ionic Currents ◽  
Time Dependent ◽  
Transient Outward Current ◽  
Whole Cell Patch Clamp ◽  
Cardiac Purkinje Fibers ◽  
Cardiac Purkinje Cells ◽  
Hyperpolarization Activated Current

Cardiac Purkinje fibers play an important role in cardiac arrhythmias, but no information is available about ionic currents in human cardiac Purkinje cells (PCs). PCs and midmyocardial ventricular myocytes (VMs) were isolated from explanted human hearts. K+ currents were evaluated at 37°C with whole cell patch clamp. PCs had clear inward rectifier K+current ( I K1), with a density not significantly different from VMs between −110 and −20 mV. A Cs+-sensitive, time-dependent hyperpolarization-activated current was measurable negative to −60 mV. Transient outward current ( I to) density was smaller, but end pulse sustained current ( I sus) was larger, in PCs vs. VMs. I to recovery was substantially slower in PCs, leading to strong frequency dependence. Unlike VM I to, which was unaffected by 10 mM tetraethylammonium, Purkinje I to was strongly inhibited by tetraethylammonium, and Purkinje I to was 10-fold more sensitive to 4-aminopyridine than VM. PC I sus was also reduced strongly by 10 mM tetraethylammonium. In conclusion, human PCs demonstrate a prominent I K1, a time-dependent hyperpolarization-activated current, and an I towith pharmacological sensitivity and recovery kinetics different from those in the atrium or ventricle and compatible with a different molecular basis.

CaM kinase augments cardiac L-type Ca2+ current: a cellular mechanism for long Q-T arrhythmias

1999 ◽  
Vol 276 (6) ◽  
pp. H2168-H2178 ◽  
Author(s):  
Yuejin Wu ◽  
Leigh B. MacMillan ◽  
R. Blair McNeill ◽  
Roger J. Colbran ◽  
Mark E. Anderson
Keyword(s):  
Ventricular Myocytes ◽  
Ryanodine Receptors ◽  
Cam Kinase ◽  
Early Afterdepolarizations ◽  
Ultrastructural Studies ◽  
Intracellular Ca ◽  
Dependent Protein ◽  
T Tubules ◽  
Rabbit Ventricular Myocytes

Early afterdepolarizations (EAD) caused by L-type Ca2+ current ( I Ca,L) are thought to initiate long Q-T arrhythmias, but the role of intracellular Ca2+ in these arrhythmias is controversial. Rabbit ventricular myocytes were stimulated with a prolonged EAD-containing action potential-clamp waveform to investigate the role of Ca2+/calmodulin-dependent protein kinase II (CaM kinase) in I Ca,L during repolarization. I Ca,L was initially augmented, and augmentation was dependent on Ca2+ from the sarcoplasmic reticulum because the augmentation was prevented by ryanodine or thapsigargin. I Ca,Laugmentation was also dependent on CaM kinase, because it was prevented by dialysis with the inhibitor peptide AC3-I and reconstituted by exogenous constitutively active CaM kinase when Ba2+ was substituted for bath Ca2+. Ultrastructural studies confirmed that endogenous CaM kinase, L-type Ca2+ channels, and ryanodine receptors colocalized near T tubules. EAD induction was significantly reduced in current-clamped cells dialyzed with AC3-I (4/15) compared with cells dialyzed with an inactive control peptide (11/15, P = 0.013). These findings support the hypothesis that EADs are facilitated by CaM kinase.

The functional role of cardiac T-tubules explored in a model of rat ventricular myocytes

2006 ◽  
Vol 364 (1842) ◽  
pp. 1187-1206 ◽  
Author(s):  
Michal Pásek ◽  
Jiři Šimurda ◽  
Georges Christé
Keyword(s):  
Ventricular Myocytes ◽  
Contractile Activity ◽  
Tubular Lumen ◽  
Current Clamp Mode ◽  
Intracellular Ca ◽  
Ionic Changes ◽  
Access Resistance ◽  
T Tubules ◽  
Tubular Membranes

The morphology of the cardiac transverse-axial tubular system (TATS) has been known for decades, but its function has received little attention. To explore the possible role of this system in the physiological modulation of electrical and contractile activity, we have developed a mathematical model of rat ventricular cardiomyocytes in which the TATS is described as a single compartment. The geometrical characteristics of the TATS, the biophysical characteristics of ion transporters and their distribution between surface and tubular membranes were based on available experimental data. Biophysically realistic values of mean access resistance to the tubular lumen and time constants for ion exchange with the bulk extracellular solution were included. The fraction of membrane in the TATS was set to 56%. The action potentials initiated in current-clamp mode are accompanied by transient K + accumulation and transient Ca 2+ depletion in the TATS lumen. The amplitude of these changes relative to external ion concentrations was studied at steady-state stimulation frequencies of 1–5 Hz. Ca 2+ depletion increased from 7 to 13.1% with stimulation frequency, while K + accumulation decreased from 4.1 to 2.7%. These ionic changes (particularly Ca 2+ depletion) implicated significant decrease of intracellular Ca 2+ load at frequencies natural for rat heart.

Antisense inhibition of Na+/Ca2+ exchange during anoxia/reoxygenation in ventricular myocytes

2001 ◽  
Vol 281 (5) ◽  
pp. H2184-H2190 ◽  
Author(s):  
B. N. Eigel ◽  
R. W. Hadley
Keyword(s):  
Guinea Pig ◽  
Antisense Oligonucleotide ◽  
Ventricular Myocytes ◽  
Antisense Inhibition ◽  
Start Site ◽  
Intracellular Ca

This study investigated the role of the Na+/Ca2+ exchanger (NCX) in regulating cytosolic intracellular Ca2+concentration ([Ca2+]i) during anoxia/reoxygenation in guinea pig ventricular myocytes. The hypothesis that the NCX is the predominant mechanism mediating [Ca2+]i overload in this model was tested through inhibition of NCX expression by an antisense oligonucleotide. Immunocytochemistry revealed that this antisense oligonucleotide, directed at the area around the start site of the guinea pig NCX1, specifically reduced NCX expression in cultured adult myocytes by 90 ± 4%. Antisense treatment inhibited evoked NCX activity by 94 ± 3% and decreased the rise in [Ca2+]i during anoxia/reoxygenation by 95 ± 3%. These data suggest that NCX is the predominant mechanism mediating Ca2+ overload during anoxia/reoxygenation in guinea-pig ventricular myocytes.

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