scholarly journals Spatially discordant alternans in cardiomyocyte monolayers

2008 ◽  
Vol 294 (3) ◽  
pp. H1417-H1425 ◽  
Author(s):  
Carlos de Diego ◽  
Rakesh K. Pai ◽  
Amish S. Dave ◽  
Adam Lynch ◽  
Mya Thu ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Ventricular Myocytes ◽  
Conduction Block ◽  
Three Dimensional ◽  
Bay K 8644 ◽  
Neonatal Rat ◽  
Two Dimensional ◽  
Nodal Lines ◽  
Dynamic Factors ◽  
Rapid Pacing

Repolarization alternans is a harbinger of sudden cardiac death, particularly when it becomes spatially discordant. Alternans, a beat-to-beat alternation in the action potential duration (APD) and intracellular Ca (Cai), can arise from either tissue heterogeneities or dynamic factors. Distinguishing between these mechanisms in normal cardiac tissue is difficult because of inherent complex three-dimensional tissue heterogeneities. To evaluate repolarization alternans in a simpler two-dimensional cardiac substrate, we optically recorded voltage and/or Cai in monolayers of cultured neonatal rat ventricular myocytes during rapid pacing, before and after exposure to BAY K 8644 to enhance dynamic factors promoting alternans. Under control conditions ( n = 37), rapid pacing caused detectable APD alternans in 81% of monolayers, and Cai transient alternans in all monolayers, becoming spatially discordant in 62%. After BAY K 8644 ( n = 28), conduction velocity restitution became more prominent, and APD and Cai alternans developed and became spatially discordant in all monolayers, with an increased number of nodal lines separating out-of-phase alternating regions. Nodal lines moved closer to the pacing site with faster pacing rates and changed orientation when the pacing site was moved, as predicted for the dynamically generated, but not heterogeneity-based, alternans. Spatial APD gradients during spatially discordant alternans were sufficiently steep to induce conduction block and reentry. These findings indicate that spatially discordant alternans severe enough to initiate reentry can be readily induced by pacing in two-dimensional cardiac tissue and behaves according to predictions for a predominantly dynamically generated mechanism.

scholarly journals Hexokinase–mitochondrial interactions regulate glucose metabolism differentially in adult and neonatal cardiac myocytes

2013 ◽  
Vol 142 (4) ◽  
pp. 425-436 ◽  
Author(s):  
Guillaume Calmettes ◽  
Scott A. John ◽  
James N. Weiss ◽  
Bernard Ribalet
Keyword(s):  
Cardiac Tissue ◽  
Ventricular Myocytes ◽  
Glycogen Synthesis ◽  
Neonatal Rat ◽  
Metabolic Profiles ◽  
Rat Ventricular Myocytes ◽  
Glycolytic Activity ◽  
Extracellular Glucose ◽  
Functional Consequences ◽  
Neonatal Rat Ventricular Myocytes

In mammalian tumor cell lines, localization of hexokinase (HK) isoforms to the cytoplasm or mitochondria has been shown to control their anabolic (glycogen synthesis) and catabolic (glycolysis) activities. In this study, we examined whether HK isoform differences could explain the markedly different metabolic profiles between normal adult and neonatal cardiac tissue. We used a set of novel genetically encoded optical imaging tools to track, in real-time in isolated adult (ARVM) and neonatal (NRVM) rat ventricular myocytes, the subcellular distributions of HKI and HKII, and the functional consequences on glucose utilization. We show that HKII, the predominant isoform in ARVM, dynamically translocates from mitochondria and cytoplasm in response to removal of extracellular glucose or addition of iodoacetate (IAA). In contrast, HKI, the predominant isoform in NRVM, is only bound to mitochondria and is not displaced by the above interventions. In ARVM, overexpression of HKI, but not HKII, increased glycolytic activity. In neonatal rat ventricular myocytes (NVRM), knockdown of HKI, but not HKII, decreased glycolytic activity. In conclusion, differential interactions of HKI and HKII with mitochondria underlie the different metabolic profiles of ARVM and NRVM, accounting for the markedly increased glycolytic activity of NRVM.

scholarly journals Anisotropic conduction block and reentry in neonatal rat ventricular myocyte monolayers

2011 ◽  
Vol 300 (1) ◽  
pp. H271-H278 ◽  
Author(s):  
Carlos de Diego ◽  
Fuhua Chen ◽  
Yuanfang Xie ◽  
Rakesh K. Pai ◽  
Leonid Slavin ◽  
...  
Keyword(s):  
Gap Junction ◽  
Conduction Block ◽  
Neonatal Rat ◽  
Fiber Direction ◽  
Ventricular Myocyte ◽  
Na Current ◽  
Current Availability ◽  
Rapid Pacing ◽  
Rat Ventricular Myocyte ◽  
Junction Conductance

Anisotropy can lead to unidirectional conduction block that initiates reentry. We analyzed the mechanisms in patterned anisotropic neonatal rat ventricular myocyte monolayers. Voltage and intracellular Ca (Cai) were optically mapped under the following conditions: extrastimulus (S1S2) testing and/or tetrodotoxin (TTX) to suppress Na current availability; heptanol to reduce gap junction conductance; and incremental rapid pacing. In anisotropic monolayers paced at 2 Hz, conduction velocity (CV) was faster longitudinally than transversely, with an anisotropy ratio [AR = CVL/CVT, where CVL and CVT are CV in the longitudinal and transverse directions, respectively], averaging 2.1 ± 0.8. Interventions decreasing Na current availability, such as S1S2 pacing and TTX, slowed CVL and CVT proportionately, without changing the AR. Conduction block preferentially occurred longitudinal to fiber direction, commonly initiating reentry. Interventions that decreased gap junction conductance, such as heptanol, decreased CVT more than CVL, increasing the AR and causing preferential transverse conduction block and reentry. Rapid pacing resembled the latter, increasing the AR and promoting transverse conduction block and reentry, which was prevented by the Cai chelator 1,2-bis oaminophenoxy ethane- N, N, N′, N′-tetraacetic acid (BAPTA). In contrast to isotropic and uniformly anisotropic monolayers, in which reentrant rotors drifted and self-terminated, bidirectional anisotropy (i.e., an abrupt change in fiber direction exceeding 45°) caused reentry to anchor near the zone of fiber direction change in 77% of monolayers. In anisotropic monolayers, unidirectional conduction block initiating reentry can occur longitudinal or transverse to fiber direction, depending on whether the experimental intervention reduces Na current availability or decreases gap junction conductance, agreeing with theoretical predictions.

Abstract 1349: Overexpression And Dominant-negative Suppression Of Inwardly Rectifying Potassium Channel Protein (Kir2.1) Alters Electrophysiology And Spiral Wave Dynamics Of An In Vitro Model Of Cardiac Myocytes

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Rajesh B Sekar ◽  
Eddy Kizana ◽  
Hee C Cho ◽  
Rachel R Smith ◽  
Brett P Eaton ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Spiral Waves ◽  
Dominant Negative ◽  
Neonatal Rat ◽  
Resting Potential ◽  
Dominant Negative Mutant ◽  
Rapid Pacing ◽  
The Stability ◽  
Inwardly Rectifying

Introduction : An important role for the inwardly rectifying potassium current (I K1 ) has been postulated in controlling the stability and frequency of rotors responsible for ventricular tachycardia and fibrillation. We investigated the effects of Kir2.1 overexpression and Kir2.1AAA dominant-negative mutant suppression on the electrophysiology and inducibility, stability and frequency of spiral waves in an in vitro cardiac tissue model. Methods/Results : Neonatal rat ventricular myocytes (NRVMs) were transduced by lentiviral vectors encoding Kir2.1 or Kir2.1AAA. Immunostaining revealed Kir2.1 or mutant Kir2.1 protein overexpression and whole cell-clamp confirmed the predicted effects on I K1 , resting potential, and action potential duration (APD 80 ). Optical mapping was performed on confluent NRVM monolayers containing a 5 mm diameter central island of gene-modified NRVMs created by a stenciling technique. APs propagated with increased CV (25.1±2.7 cm/sec, n=7) and shortened APD 80 (73±11 msec, n=7) in islands of Kir2.1 overexpression, or decreased CV (13.1±1.1 cm/sec, n=7) and prolonged APD 80 (263±14 msec, n=7) in islands of Kir2.1AAA suppression, compared with normal CV and APD 80 of 19.2±0.4 cm/sec and 169±14 msec (n=7) in non-transduced islands. Reentry was initiated by rapid pacing. With Kir2.1 overexpression, reentrant waves anchored to the island and remained stable (89±15 minutes, n=3) with a frequency of 8±2 Hz. Superfusion with 0.5 mM BaCl 2 to block I K1 slowed reentry to 1 Hz and terminated it shortly after initiation. NRVM monolayers with islands of Kir2.1AAA suppression (n=3) displayed rapid spontaneous activity. Rapid pacing of these monolayers initiated an unstable figure-of-eight reentry (n=3) that degraded into single and multi-armed spiral waves, anchored to varying parts of the island with a maximum frequency of 2±1 Hz. Importantly, no reentry could be initiated in monolayers with non-transduced islands (n=3). Conclusion : Functional reentrant waves induced by rapid pacing are anchored to islands of localized Kir2.1 overexpression whereas they drop in frequency and meander in islands of dominant-negative suppression of Kir2.1, confirming the importance of I K1 for the stability of these waves in cardiac tissue.

Dynamic changes of cardiac conduction during rapid pacing

2007 ◽  
Vol 292 (4) ◽  
pp. H1796-H1811 ◽  
Author(s):  
Aleksandar A. Kondratyev ◽  
Julien G. C. Ponard ◽  
Adelina Munteanu ◽  
Stephan Rohr ◽  
Jan P. Kucera
Keyword(s):  
Ventricular Myocytes ◽  
Conduction Block ◽  
Pump Current ◽  
Neonatal Rat ◽  
Cardiac Conduction ◽  
Dynamic Changes ◽  
Abrupt Decrease ◽  
Rate Dependent ◽  
Ionic Mechanisms ◽  
Inward Currents

Slow conduction and unidirectional conduction block (UCB) are key mechanisms of reentry. Following abrupt changes in heart rate, dynamic changes of conduction velocity (CV) and structurally determined UCB may critically influence arrhythmogenesis. Using patterned cultures of neonatal rat ventricular myocytes grown on microelectrode arrays, we investigated the dynamics of CV in linear strands and the behavior of UCB in tissue expansions following an abrupt decrease in pacing cycle length (CL). Ionic mechanisms underlying rate-dependent conduction changes were investigated using the Pandit-Clark-Giles-Demir model. In linear strands, CV gradually decreased upon a reduction of CL from 500 ms to 230–300 ms. In contrast, at very short CLs (110–220 ms), CV first decreased before increasing again. The simulations suggested that the initial conduction slowing resulted from gradually increasing action potential duration (APD), decreasing diastolic intervals, and increasing postrepolarization refractoriness, which impaired Na+ current ( INa) recovery. Only at very short CLs did APD subsequently shorten again due to increasing Na+/K+ pump current secondary to intracellular Na+ accumulation, which caused recovery of CV. Across tissue expansions, the degree of UCB gradually increased at CLs of 250–390 ms, whereas at CLs of 180–240 ms, it first increased and subsequently decreased. In the simulations, reduction of inward currents caused by increasing intracellular Na+ and Ca2+ concentrations contributed to UCB progression, which was reversed by increasing Na+/K+ pump activity. In conclusion, CV and UCB follow intricate dynamics upon an abrupt decrease in CL that are determined by the interplay among INa recovery, postrepolarization refractoriness, APD changes, ion accumulation, and Na+/K+ pump function.

Time-reversal-breaking Weyl nodal lines in two-dimensional A3C2 (A = Ti, Zr, Hf) intrinsically ferromagnetic materials with high Curie temperature

Nanoscale ◽  
2021 ◽  
Author(s):  
Feng Zhou ◽  
Ying Liu ◽  
Minquan KUANG ◽  
Peng Wang ◽  
Jianhua WANG ◽  
...  
Keyword(s):  
Curie Temperature ◽  
Time Reversal ◽  
Three Dimensional ◽  
Ferromagnetic Materials ◽  
High Curie Temperature ◽  
Two Dimensional ◽  
Nodal Lines ◽  
Spin Polarized

Most materials that feature nontrivial topological band topology are spin-degenerate and three dimensional, strongly restricting them from application in spintronic nanodevices. Hence, two-dimensional (2D) intrinsically spin-polarized systems with rich topological...

BAY K 8644 depresses excitation-contraction coupling in cardiac muscle

1996 ◽  
Vol 270 (3) ◽  
pp. C878-C884 ◽  
Author(s):  
E. McCall ◽  
D. M. Bers
Keyword(s):  
Cardiac Tissue ◽  
Ventricular Myocytes ◽  
Cell Voltage ◽  
Bay K 8644 ◽  
Ca Channel ◽  
Ca Current ◽  
Release Channel ◽  
Dihydropyridine Receptors ◽  
Current Voltage ◽  
The Relationship

We determined the effect of the dihydropyridine L-type Ca channel agonist BAY K 8644 (BAY) on excitation-contraction (E-C) coupling in isolated ferret ventricular myocytes using whole cell voltage clamp. The sarcoplasmic reticulum (SR) Ca load during the test pulses, assessed by caffeine-induced contractures, was similar in the presence and absence of BAY, with extracellular Ca concentration lowered from 3 to 1 mM in BAY. The relationship between L-type Ca current (ICa) and contraction was assessed, with current and contractions measured during depolarizations from -40 to between -30 and +50 mV after a conditioning train (to ensure constant SR Ca load). BAY shifted the current-contraction relationship downward, such that, for a given ICa and SR Ca load, the contraction elicited was much smaller in the presence of BAY. BAY also induced a characteristic negative shift in the the current-voltage relationship. We conclude that BAY decreases the efficacy of a given Ca current to induce SR Ca release during E-C coupling in ferret cardiac tissue (in contrast to the BAY-induced increase of resting SR Ca release). This may reflect an alteration in the state of the SR Ca release channel due to BAY binding to dihydropyridine receptors.

Cardiac tissue engineering: characteristics of in unison contracting two- and three-dimensional neonatal rat ventricle cell (co)-cultures

Biomaterials ◽  
2002 ◽  
Vol 23 (24) ◽  
pp. 4793-4801 ◽  
Author(s):  
M.J.A van Luyn ◽  
R.A Tio ◽  
X.J Gallego y van Seijen ◽  
J.A Plantinga ◽  
L.F.M.H de Leij ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cardiac Tissue ◽  
Three Dimensional ◽  
Cardiac Tissue Engineering ◽  
Neonatal Rat ◽  
Engineering Characteristics ◽  
Rat Ventricle

scholarly journals Two-dimensional higher-order topology in monolayer graphdiyne

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Eunwoo Lee ◽  
Rokyeon Kim ◽  
Junyeong Ahn ◽  
Bohm-Jung Yang
Keyword(s):  
Tight Binding ◽  
Three Dimensional ◽  
Higher Order ◽  
Order Topology ◽  
Two Dimensional ◽  
First Principles Calculations ◽  
Charge Accumulation ◽  
Binding Model ◽  
Nodal Lines ◽  
Bulk Band

AbstractBased on first-principles calculations and tight-binding model analysis, we propose monolayer graphdiyne as a candidate material for a two-dimensional higher-order topological insulator protected by inversion symmetry. Despite the absence of chiral symmetry, the higher-order topology of monolayer graphdiyne is manifested in the filling anomaly and charge accumulation at two corners. Although its low energy band structure can be properly described by the tight-binding Hamiltonian constructed by using only the pz orbital of each atom, the corresponding bulk band topology is trivial. The nontrivial bulk topology can be correctly captured only when the contribution from the core levels derived from px,y and s orbitals are included, which is further confirmed by the Wilson loop calculations. We also show that the higher-order band topology of a monolayer graphdyine gives rise to the nontrivial band topology of the corresponding three-dimensional material, ABC-stacked graphdiyne, which hosts monopole nodal lines and hinge states.

Abstract 38: Simultaneous Optical Pacing and Optical Voltage Mapping in Optogenetic Neonatal Rat Ventricular Myocyte Cultures

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Qince Li ◽  
KahYong Goh ◽  
Wei Kong ◽  
Ruby R Ni ◽  
Vladimir Fast ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Ventricular Myocytes ◽  
Cell Activity ◽  
Neonatal Rat ◽  
Innovative Technology ◽  
Cell Toxicity ◽  
Cardiovascular Research ◽  
Precise Control ◽  
Culture Model ◽  
Living Tissues

Optogenetics is an emerging technology allowing remote and precise control of cell activity in living tissues. Despite its rapid advancements, application of this innovative technology to cardiovascular research is still limited, in part due to shortage of optogenetic cardiac tissue models and compatible imaging methods. The present study aimed to develop an optogenetic culture model using neonatal rat ventricular myocytes (NRVM) expressing light-gated Channelrhodopsin-2 (ChR2) and characterize activation spread during optical stimulation using optical mapping of membrane potential (Vm). Primary NVRM cultures were infected with lentivirus containing ChR2 gene. Cultures were paced electrically or optically with pulses of blue (470 nm) LED light. Activation spread was simultaneously mapped using Vm-sensitive dye (RH-237) and a photodiode mapping system. Results showed that ChR2 could be readily transduced to NRVMs by the lentiviral method; however, high-level ChR2 expression was associated with substantial cell toxicity. Lower ChR2 expression, achieved by administration of bromodeoxyuridine, had minor effects on cell morphology and function while allowing optical pacing at frequencies of 0.5-3 Hz. Simultaneous Vm mapping showed that conduction velocity, APD80, and dV/dtmax were similar in optogenetic and control cultures. Finally, the optogenetic cultures could be optically paced at multiple sites, leading to significantly reduced overall activation time. In summary, we demonstrated that ChR2 expression can cause cell toxicity in NRVM cultures but the toxicity can be mitigated allowing optical pacing and simultaneous optical activation mapping without significant impairment of electrophysiological function. This optogenetic cardiac culture model expands the availability of optogenetic tools for cardiac research.

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