Transient Decay Time Research Articles

Preparation of nanoporous BiVO4/TiO2/Ti film through electrodeposition for photoelectrochemical water splitting.

A nanoporous BiVO4/TiO2/Ti film was successfully fabricated by electrodepositing a nanoporous BiOI film on nanoporous TiO2 arrays followed by annealing at 450°C for 2 h. The electrodeposition of BiOI film was carried out at different times (10, 30, 100, 500 and 1000 s) in Bi(NO3)3 and KI solution. The morphological, crystallographic and photoelectrochemical properties of the prepared BiVO4/TiO2/Ti heterojunction film were examined by using different characterization techniques. UV–vis spectrum absorption studies confirmed an increase in absorption intensities with increasing electrodeposition time, and the band gap of BiVO4/TiO2/Ti film is lower than that of TiO2/Ti. The photocatalytic efficiency of BiVO4/TiO2/Ti heterojunction film was higher compared to that of the TiO2/Ti film owing to the longer transient decay time for BiVO4/TiO2/Ti film (3.2 s) than that of TiO2/Ti film (0.95 s) in our experiment. The BiVO4/TiO2/Ti heterojunction film prepared by electrodeposition for 1000 s followed by annealing showed a high photocurrent density of 0.3363 mA cm−2 at 0.6 V versus saturated calomel electrode. Furthermore, the lowest charge transfer resistance from electrochemical impedance spectroscopy was recorded for the BiVO4/TiO2/Ti film (1000 s) under irradiation.

Abstract 12: M6A Modification in RNA Regulates Cardiomyocyte and Cardiac Function in Heart Failure

Background: Adenosine in RNA is a substrate for addition or removal of methyl group. Reported five decades ago, methylated adenosine (m6A), the most abundant and functionally relevant chemical modification in RNA, whose transcriptome-wide mapping became possible only recently due to next generation sequencing (NGS). Coupled with NGS, m6A-methylated RNA capture (MeRIP-seq) identified widespread m6A distribution in ~8000 mRNA and ~1000 lncRNA transcripts in human and mouse transcriptome. Methods and Results: In a first of its kind approach, we examined m6A RNA methylation in both failing and non-failing hearts. We discovered that global m6A RNA methylation is significantly higher in left ventricles (LV) of failing human, swine and mouse hearts as compared to non-failing controls. Increase in m6A was associated with significantly lower expression of one of the key m6A demethylases, FTO, in the ischemic heart. siRNA-mediated silencing of FTO resulted in significant arrhythmias, loss of Ca 2+ dynamics such as Ca 2+ transient decay (Tau) and cardiomyocyte relaxation time in isolated adult rat cardiomyocytes. Conversely, FTO gene transfer reduced m6A and improved Ca 2+ transients and contractile function in primary cardiomyocytes under hypoxia. In a mouse model of MI, AAV-mediated gene transfer of FTO significantly improved cardiac function post-MI. We identified transcriptome-wide m6A distribution signatures and conserved methylated sites of several mRNAs and lncRNAs using MeRIP-seq in both human and mouse failing and non-failing LV. Detailed MeRIP map of individual transcripts identified differentially methylated 3’-UTR, 5’-UTR and exon sites within several cardiac mRNAs that are important for cardiac function. Conclusion: Our data provide first evidence that m6A modification in RNA is a regulator of cardiomyocyte Ca 2+ dynamics and cardiac function. Our findings on the dynamic nature of the cardiac m6A-epitranscriptome will add another portfolio to mRNA and lncRNA regulation of cardiac remodeling.

QRS/T-wave and calcium alternans in a type I diabetic mouse model for spontaneous postmyocardial infarction ventricular tachycardia: A mechanism for the antiarrhythmic effect of statins

The incidence of sudden arrhythmic death is markedly increased in diabetics. The purpose of this study was to develop a mouse model for postmyocardial infarction (post-MI) ventricular tachycardia (VT) in the diabetic heart and determine the mechanism of an antiarrhythmic effect of statins. ECG transmitters were implanted in wild-type (WT), placebo, and pravastatin-treated type I diabetic Akita mice. MIs were induced by coronary ligation, and Ca2+ transients were studied by optical mapping, and Ca2+ transients and sparks in left ventricular myocytes (VM) by the Ionoptix system and confocal microscopy. Burst pacing of Akita mouse hearts resulted in rate-related QRS/T-wave alternans, which was attenuated in pravastatin-treated mice. Post-MI Akita mice developed QRS/T-wave alternans and VT at 2820 ± 879 beats per mouse, which decreased to 343 ± 115 in pravastatin-treated mice (n = 13, P <.05). Optical mapping demonstrated pacing-induced VT originating in the peri-infarction zone and Ca2+ alternans, both attenuated in hearts of statin-treated mice. Akita VM displayed Ca2+ alternans, and triggered activity as well as increased Ca2+ transient decay time (Tau), Ca2+ sparks, and cytosolic Ca2+ and decreased SR Ca2+ stores all of which were in part reversed in cells from statin treated mice. Homogenates of Akita ventricles demonstrated decreased SERCA2a/PLB ratio and increased ratio of protein phosphatase (PP-1) to the PP-1 inhibitor PPI-1 which were reversed in homogenates of pravastatin-treated Akita mice. Pravastatin decreased the incidence of post-MI VT and Ca2+ alternans in Akita mouse hearts in part by revering abnormalities of Ca2+ handling via the PP-1/PPI-1 pathway.

Photodoping-Driven Crossover in the Low-Frequency Noise of MoS2 Transistors

Transition metal dichalcogenide field-effect transistors (FETs) have been actively explored for low-power electronics, light detection, and sensing. Albeit promising, their performance is strongly limited by low-frequency noise (LFN). Here, we report on the study of LFN in MoS$_2$ FETs on SiO$_2$ substrates in ambient conditions using photodoping. Using this external excitation source allows us to access different non-equilibrium steady states and cross over different noise regimes. We observe a dependence of the noise power spectrum with the transient decay time window, approaching $1/f$-type when the system is closer to equilibrium, and identify a dependence of the LFN with channel thickness. Monolayer/bilayer devices exhibit random telegraph noise for insulating regimes and $1/f$-type Hooge mobility fluctuations (HMF) for conductive regimes. Thicker devices exhibit mainly $1/f$-type carrier number fluctuations (CNF). In the latter, we observe a photodoping-induced change from a near parabolic to a near linear dependence of the inverse $1/f$ noise amplitude above the threshold gate voltage. This change indicates a crossover in the LFN mechanism from CNF to HMF. We demonstrate that the study of conductance and noise under photodoping is an effective tool to identify dominating carrier noise mechanisms in few-atomic-layer FETs for a wide range of doping regimes.

Dissection of the Effects of Quercetin on Mouse Myocardium.

Quercetin is a plant flavonoid with several biological activities. This study aimed to describe quercetin effects on contractile and electrophysiological properties of the cardiac muscle as well as on calcium handling. Quercetin elicited positive inotropism that was significantly reduced by propranolol indicating an involvement of the sympathetic nervous system. In cardiomyocytes, 30 μM quercetin increased ICa,L at 0 mV from -0.95 ± 0.01 A/F to -1.21 ± 0.08 A/F. The membrane potential at which 50% of the channels are activated (V0.5 ) shifted towards more negative potentials from -13.06 ± 1.52 mV to -19.26 ± 1.72 mV and did not alter the slope factor. Furthermore, quercetin increased [Ca2+ ]i transient by 28% when compared to control. Quercetin accelerated [Ca2+ ]i transient decay time, which could be attributed to SERCA activation. In resting cardiomyocytes, quercetin did not change amplitude or frequency of Ca2+ sparks. In isolated heart, quercetin increased heart rate and decreased PRi, QTc and duration of the QRS complex. Thus, we showed that quercetin activates β-adrenoceptors, leading to increased L-type Ca2+ current and cell-wide intracellular Ca2+ transient without visible changes in Ca2+ sparks.

InGaN/GaN light-emitting diode having direct hole injection plugs and its high-current operation.

The light-emitting diode (LED) with an improved hole injection and straightforward process integration is proposed. p-type GaN direct hole injection plugs (DHIPs) are formed on locally etched multiple-quantum wells (MQWs) by epitaxial lateral overgrowth (ELO) method. We confirm that the optical output power is increased up to 23.2% at an operating current density of 100 A/cm2. Furthermore, in order to identify the origin of improvement in optical performance, the transient light decay time and light intensity distribution characteristics were analyzed on the DHIP LED devices. Through the calculation of the electroluminescence (EL) decay time, internal quantum efficiency (IQE) is extracted along with the recombination parameters, which reveals that the DHIPs have a significant effect on enhancement of radiative recombination and reduction of efficiency droop. Furthermore, the mapping PL reveals that the DHIP LED also has a potential to improve the light extraction efficiency by hexagonal pyramid shaped DHIPs.

Tunable transient decay times in nonlinear systems: Application to magnetic precession

The dynamical motion of the magnetization plays a key role in the properties of magnetic materials. If the magnetization is initially away from the equilibrium direction in a magnetic nanoparticle, it will precess at a natural frequency and, with some damping present, will decay to the equilibrium position in a short lifetime. Here we investigate a simple but important situation where a magnetic nanoparticle is driven non-resonantly by an oscillating magnetic field, not at the natural frequency. We find a surprising result that the lifetime of the transient motion is strongly tunable, by factors of over 10000, by varying the amplitude of the driving field.

Abstract 20209: Spontaneous Post Myocardial Infarction Arrhythmia is Potentiated by Calcium Alternans in Type I Diabetic Akita Mice

Introduction: Myocardial infarction (MI) is the most common cause of mortality in diabetes. Diabetics have been shown to be twice as likely to die suddenly from MI out of hospital compared to non diabetic patients. The mechanism of sudden death in the diabetic population is unclear. Here we use the Akita Type I diabetic mouse as an animal model for the study of post MI ventricular tachycardia arrhythmias (VT) and the role of abnormalities of Ca2+ homeostasis in the pathogenesis of post MI VT. Methods: To determine the effect of MI on the incidence of VT, EKG transmitters were implanted into WT and Akita mice. MIs were generated by permanent ligation of the left coronary artery resulting in infarctions affecting more than 30% of the LV as demonstrated by echocardiographic analysis and TTC staining. Dual calcium-voltage optical mapping was performed on the isolated Langendorf heart after MI. Left ventricular myocytes were isolated for calcium imaging studies. Sarcomere shortening and Ca2+transients were measured by Ionoptix system and Ca2+ sparks by confocal microscopy. Results: Compared to WT, Akita diabetic mice developed a high incidence of non sustained and sustained VT in the first 30h post MI peaking at 18 h. Epicardial optical mapping demonstrated pacing induced: Ca2+ alternans which was most marked in the peri-infarction zone of Akitas and VT also originating in the peri-infarction zone in the Akita mice, but not in WT. Single cardiomyocytes from Akita displayed both contractile and Ca2+ alternans when pacing rate was increased above 3Hz, but none in cells from WT mice. Ca2+ imaging studies were performed to determine whether alterations in Sacroplasmic reticulum(SR) Ca2+ function contributes to Ca2+ alternans. In Akita myocytes, Ca2+ transient decay time( Tau) was significantly increased ( 0.171±0.01s, N=23 ) compared to WT(0.139±0.007s, N=20, P&lt;0.05), The frequency of spontaneous Ca2+ sparks in Akita mocytes increased from 0.043 ± 0.003 sparks/100μm/s (N=23) in the WT to 0.266 ± 0.023 sparks/100μm/s ( P&lt;0.05, N=36). Conclusions: The type 1 diabetic Akita mice demonstrate a high incidence of spontaneous post MI VT associated with pronounced Ca2+ alternans in the peri-infarction zone and abnormalities of Ca2+ homeostasis.

Synthesis of NiGa2O4 Octahedron Nanocrystal with Exposed {111} Facets and Enhanced Efficiency of Photocatalytic Water Splitting

AbstractFor the first time, octahedral NiGa2O4 nanocrystals having reactive pH‐dependent {111} facets are synthesized through a facile hydrothermal route without using any template or organic surfactant. The {111} facets of octahedral NiGa2O4 display clearly enhanced photocatalytic generation of hydrogen and oxygen from water splitting and good photocatalytic stability. Density functional calculations suggest that mixed statistically occupied Ga/Ni (fourfold‐ and sixfold‐coordinated Ga/Ni) are most likely to be exposed at the (111) surface of NiGa2O4, which is very favorable for enhancing the photocatalytic activities, and the photoelectrochemical properties show that the NiGa2O4 octahedron displays a better photocurrent than NiGa2O4 nanorods with the [100] growth direction. The transient photocurrent decay scan results demonstrate that the NiGa2O4 octahedron exposed {111} facet electrode exhibits a transient decay time of 4 s, whereas this time is only 2 s for NiGa2O4 nanorod electrodes with the [100] growth direction. This longer transient decay time indicates that the charge‐carrier recombination rate is lower in the NiGa2O4 octahedron electrode, which will contribute to the enhancement of the photocatalytic activity. The present study also demonstrates that designing nanostructures with the appropriate morphology and surface structures is a feasible approach for enhancing the photoexcited charge‐transfer lifetime and developing highly active semiconductor photocatalysts.

Influence of host matrix on thermally-activated delayed fluorescence: Effects on emission lifetime, photoluminescence quantum yield, and device performance

The influence of the host molecules on the photoluminescent (PL) and electroluminescent (EL) properties of organic light-emitting diode (OLED) emitters showing efficient thermally-activated delayed fluorescence (TADF) has yet to be investigated in detail. Here we demonstrate that the choice of host can cause large variations in the PL quantum yield (ΦPL∼15–70%) and delayed PL transient decay (τdel∼2–70ms) of a spiro-acridine-based TADF guest. We show that the effect of exciplex formation on ΦPL must be considered even at low concentrations of the TADF guest. Using the same TADF guest but changing the host layer, we are able to greatly vary the PL transient decay time from ∼4 to ∼70ms while maintaining a high ΦPL ∼70%, which can lead to new applications. Detailed spectral characterization during PL decay reveals a gradually increasing singlet–triplet energy gap (ΔEST) as the origin of these observations. The time-varying ΔEST is explained based on dipole interactions between the host and guest molecules. Finally, PL and electrical considerations for host selection are discussed based on the performance of OLED devices.

Dysregulation of intracellular Ca2+ in lymphocytes and neutrophils in type 2 diabetic patients (1072.11)

Background: Patients with T2D are immune‐compromised, making them more susceptible to infections and long term complications than non‐diabetic individuals. Neutrophils and lymphocytes play key roles in host‐immune responses to infections, and their phagocytic and chemotatic activities are reduced in diabetes. To date, the underlying causes for impairment in neutrophils and lymphocytes functions in T2D remain poorly defined. Dysregulation of intracellular Ca2+ cycling is a common phenotype in many diabetic cells. This study investigated if intracellular Ca2+ cycling is also defective in neutrophils and lymphocytes isolated from individuals with T2D.Methods and results: Neutrophils and lymphocytes were obtained from patients with T2D and healthy controls with consent, and their intracellular Ca2+ cycling kinetics when challenged with thapsigargin (TG), formyl‐methionyl‐leucyl‐phenylalanine (fMLP) and hydrogen peroxide (H2O2), were compared using time‐lapsed Ca2+ imaging assays. All cells from T2D and control patients responded to TG, fMLP and H2O2. However, the rate of cytoplasmic Ca2+ rise, peak Ca2+ transient amplitude and Ca2+ transient decay times were significantly compromised in neutrophils and lymphocytes from T2D patients compared to healthy controls.Conclusion: From these data we concluded that neutrophils and lymphocytes from T2DM patients are less responsive to this wide array of intracellular Ca2+ mobilizing agonists compared to control. Moreover, the decreased [Ca2+]i in immune cells might be one of the possible mechanisms of impaired immunity in diabetic patients.

P38α regulates SERCA2a function

cAMP-dependent protein kinase (PKA) regulates the L-type calcium channel, the ryanodine receptor, and phospholamban (PLB) thereby increasing inotropy. Cardiac contractility is also regulated by p38 MAPK, which is a negative regulator of cardiac contractile function. The aim of this study was to identify the mechanism mediating the positive inotropic effect of p38 inhibition. Isolated adult and neonatal cardiomyocytes and perfused rat hearts were utilized to investigate the molecular mechanisms regulated by p38. PLB phosphorylation was enhanced in cardiomyocytes by chemical p38 inhibition, by overexpression of dominant negative p38α and by p38α RNAi, but not with dominant negative p38β. Treatment of cardiomyocytes with dominant negative p38α significantly decreased Ca2+-transient decay time indicating enhanced sarco/endoplasmic reticulum Ca2+-ATPase function and increased cardiomyocyte contractility. Analysis of signaling mechanisms involved showed that inhibition of p38 decreased the activity of protein phosphatase 2A, which renders protein phosphatase inhibitor-1 phosphorylated and thereby inhibits PP1. In conclusion, inhibition of p38α enhances PLB phosphorylation and diastolic Ca2+ uptake. Our findings provide evidence for novel mechanism regulating cardiac contractility upon p38 inhibition.

Protein Restriction after Weaning Modifies the Calcium Kinetics and Induces Cardiomyocyte Contractile Dysfunction in Rats

Protein restriction (PR) is associated with cardiovascular diseases. The purpose of this study was to investigate the effects on single ventricular cardiomyocyte contractile function of a short-term PR after weaning. Male Fischer rats that were 28 days old were randomly divided into a control group (CG, n = 16) and a protein-restricted group (PRG, n = 16). After weaning, CG and PRG animals received isocaloric diets containing 15 and 6% protein, respectively, for 35 days. Biometric parameters were then measured, and the hearts were removed for the analysis of contractile function and calcium transient in isolated cardiomyocytes of the left ventricule (LV), and the quantification of calcium and collagen fibers in LV myocardium. PRG animals had lower body weight (BW) and LV weight (LVW), an increased LVW to BW ratio and a higher proportion of collagen fibers than CG animals. PRG animals exhibited reduced tissue levels of calcium, reduced the length, width and volume of cardiomyocytes and their sarcomere length compared to CG animals. Cardiomyocytes from PRG animals had a lower amplitude of shortening, a slower time to the peak of shortening and a longer time to half-relaxation than those from the CG. Cardiomyocytes from PRG animals also presented a lower peak of calcium transient and a longer calcium transient decay time than CG animals. Taken together, the results indicate that short-term PR after weaning induces a marked structural remodeling of the myocardium parenchyma and stroma that coexists with contractile dysfunctions in single LV cardiomyocytes of rats, which is probably associated with pathological changes of the intracellular calcium kinetics, rather than inadequate available amounts of this mineral in cardiac tissue.

Abstract 163: Inhibition of p38a Regulates SERCA2a Function

Rationale: p38 MAPK is a negative regulator of cardiac contractile function, but the underlying molecular mechanism is not well understood. Objective: To determine the molecular mechanism mediating the positive inotropic effect of p38 inhibition. Methods and Results: The effect of p38 inhibition on calcium regulatory proteins and calcium cycling was investigated in isolated neonatal and adult rodent cardiomyocytes using chemical inhibitors, recombinant adenoviruses and RNAi. Chemical inhibition of p38 enhanced phospholamban (PLB) phosphorylation at serine 16 residue. This was recapitulated with dominant negative p38α adenovirus and by p38α RNAi, but not with dominant negative p38β adenovirus. Chemical inhibition of p38 and dominant negative p38α resulted in significant decrease in Ca 2+ -transient decay time in adult rat cardiomyocytes. Inhibition of p38α, but not p38β, induced an increase in phosphorylation of protein phosphatase inhibitor-1 at the protein kinase A site threonine 35. Analysis of underlying mechanisms revealed that p38 inhibition increased phosphorylation of G protein-coupled receptor kinase 2 (GRK2), but not GRK3 or GRK5. p38 inhibition- induced PLB phosphorylation was abolished in cardiomyocytes overexpressing wild type GRK2. In contrast, increased PLB phosphorylation upon p38 inhibition was not reduced in cardiomyocytes overexpressing GRK2 harboring a non-phosphorylatable mutation in serine 670 residue. Finally, p38 inhibition-induced shortening of Ca 2+ -transient decay time was absent in cardiomyocytes overexpressing wild type GRK2. Conclusions: Inhibition of p38α regulates protein phosphatase inhibitor-1 resulting in increased PLB phosphorylation and enhanced SERCA2a function.

Electron Diffraction Studies of Structural Dynamics of Bismuth Nanoparticles

The lattice response of bismuth nanoparticles to femtosecond laser excitation is probed by ultrafast electron diffraction. The transient decay time after laser excitation is observed to be longer for diffraction from the (012) lattice planes compared to that from (110). From the position of the (012) diffraction peak, a transient lattice contraction due to hot electron blast force is observed over several picoseconds followed by expansion while the position of the (110) peak shows only expansion. The diffraction peak width indicates partial disorder of the nanoparticles consistent with formation of a liquid shell as the lattice is heated.

Transient and steady-state dark current mechanisms in amorphous selenium avalanche radiation detectors

A theoretical model for describing bias-dependent transient and steady-state behaviors of dark current in amorphous selenium (a-Se) avalanche detector structures has been developed. The analytical model considers bulk thermal generation current from mid-gap sates, transient carrier depletion, and carrier injection from the electrodes incorporating avalanche multiplication. The proposed physics-based dark current model is compared with the published experimental results on three potential a-Se avalanche detector structures. The steady-state dark current is the minimum for the structures that have effective blocking layers for both holes and electrons. The transient decay time to reach a plateau decreases considerably with increasing electric field.

Increased Inducibility of Ventricular Tachycardia in the Type I Diabetic Akita Mouse is Associated with Abnormalities of Ca2+ Homeostasis and Reversed by Pravastatin.

Diabetes mellitus is associated with increased risk of sudden cardiac death. It's relationship to the development of Ventricular Tachycardia (VT) is not understood. It has recently been suggested that Inhibitors of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (statins) might exert anti arrhythmic effects. It is hypothesized that treatment of Type I diabetic Akita mice with Pravastatin decreases the inducibility of VT. Inducibility of VT in Akita mice in response to programmed ventricular stimulation was significantly increased (78.6%) compared to WT (28.6%, p=0.006). Pravastatin treatment for one week (i.p. 20mg/day) decreased the inducibility of VT to 36.84% (p&lt;0.01). Whole cell patch clamp studies of isolated ventricular myocytes from Akita mice demonstrated a high frequency of early and delayed afterdepolarizations ( EADs and DADs) compared to WT type. Pravastatin treatment significantly decreased occurrence of EADs and DADs. Ca2+ reuptake as measured by Ca2+ transient decay time (Tau) was increased in cells from Akita (170.9±10.3 ms) vs WT (138.6±7.3ms, p&lt;0.05) and cytosolic free Ca2+ was increased. Pravastatin significantly improved SR Ca2+ reuptake (Tau=142±5.9ms, p&lt;0.05), decreased cytosolic free Ca2+. Hence Pravastatin might exert and anti‐arrhythmic effect in Type I diabetes by improving Ca2+ homeostasis.

Post-Myocardial Infarction Exercise Training Reverses Cardiac Excitation-Contraction Coupling Abnormalities by Activating Cytoplasmic CaMKII

Post-myocardial infarction (MI) heart failure (HF) leads to abnormal excitation-contraction-coupling (ECC) causing cardiac dysfunctions attributable to hyper-activation of CaMKII. In contrast, exercise improves ECC in post-MI HF, but whether this is through CaMKII remains unknown. Our purpose was to test whether exercise reverses ECC dysfunction in post-MI HF through modulation of CaMKII. Permanent coronary artery ligation leading to HF was induced in Wistar rats. Four weeks after, regular treadmill running started (MI-TRN, n=14). Sham-operated (SHAM, n=12) and sedentary MI-HF (MI-SED, n=16) served as controls. MI-HF reduced exercise capacity 16% (p<0.01); exercise normalised this. Contractile function of twitch-stimulated cardiomyocytes was assessed using edge-detection and Fura-2 fluorescence microscopy with and without the CaMK inhibitor AIP (5uM). MI reduced contraction 40% (p<0.01) and increased contraction-relaxation times. This was explained by reduced Ca2+ transient amplitude and increased Ca2+ rise-decay times. Exercise corrected contraction and contraction-relaxation times, and improved Ca2+ handling. AIP abolished the exercise-induced improvement in contraction and Ca2+ transient amplitude (both p<0.01) and impaired relaxation and Ca2+ transient decay times (p<0.01) more in MI-TRN than MI-SED. Spontaneous Ca2+ waves and sparks were linescan confocal imaged in Fluo-3-loaded cardiomyocytes at normal (1.8mM) and high (5mM) extracellular Ca2+. MI increased wave frequency 65% and amplitude 21% (p<0.01); this was more pronounced at high Ca2+ and reversed by exercise. MI and AIP had no effect on sparks but they were elevated by exercise (p<0.01). AIP had no effect on Ca2+ wave frequency in MI-SED but increased frequency and amplitude in MI-TRN (p<0.05). In conclusion, CaMKII modulated exercise-induced improvements in cardiomyocyte function following MI-HF. In particular, exercise improved sarcoplasmic reticulum (SR) Ca2+-uptake and SR-loading by activating CaMKII, whereas Ca2+ release parameters were less affected. This suggests that exercise activated cytoplasmic, but not dyadic CaMKII.

Inhibition of Na+ channels ameliorates arrhythmias in a drug-induced model of Andersen-Tawil syndrome

Andersen-Tawil syndrome (ATS1)-associated ventricular tachycardias (VTs) are initiated by frequent, hypokalemia-exacerbated, premature ventricular activity (PVA). We previously demonstrated that a guinea pig model of drug-induced ATS1 (DI-ATS1) evidenced increased arrhythmias from regions with high Na(+)/Ca(2+)-exchange expression. Therefore, we hypothesize that reduced cytosolic Na(+) entry through either cardiac isoform of or tetrodotoxin (TTX)-sensitive Na(+) channels during DI-ATS1 can ameliorate arrhythmia burden. DI-ATS1 was induced with 10 μM BaCl(2) and 2 mM extracellular K(+). Ca(2+) transients and conduction velocity (CV) were optically mapped with indo-1 and di-4-ANEPPS, respectively, from Langendorff-perfused guinea pig ventricles. Nonselective Na(+) channel blockade with 1 μM flecainide reduced amplitude (Ca(A)), slowed left ventricular CV, reduced tissue excitability, and abolished the incidence of VT while decreasing the incidence of PVA relative to DI-ATS1. Selective, TTX-sensitive Na(+) channel blockade with TTX (100 nM) during DI-ATS1 decreased Ca(A) and decreased the inducibility of VTs and PVA relative to DI-ATS1 without slowing CV. Ranolazine altered Ca(A), left ventricular CV, tissue excitability, and reduced inducibility of VT and PVA in a concentration-dependent manner. None of the aforementioned interventions altered diastolic Ca(2+) levels or Ca(2+) transient decay time constant. These data suggest that cytosolic Na(+) entry and its modulation of Ca(2+) handling are necessary for arrhythmogenesis. During the loss of inward-rectifier K(+) current function, not only Na(+)/Ca(2+)-exchange dominance but Na(+) flux may determine arrhythmia burden. Therefore, selective inhibition of TTX-sensitive Na(+) channels may offer a potential therapeutic target to alleviate arrhythmias during states of Ca(2+) overload secondary to loss of inward-rectifier K(+) current function without compromising the excitability reserve.

Anisotropic response of nanosized bismuth films upon femtosecond laser excitation monitored by ultrafast electron diffraction

The lattice response of 5 nm thick bismuth film to femtosecond laser excitation is probed by ultrafast electron diffraction. The transient decay time after laser excitation is greater for diffraction from (012) lattice planes compared to (110) planes and is reduced for both planes with the increased laser fluence. These results indicate that different energy coupling mechanisms to the lattice occur depending on the crystal direction. The behavior of the diffraction peak width indicates partial disorder of the film upon photoexcitation that increases together with the laser fluence.