From an analysis of genomic sequences for bornavirus strains isolated at different time points, the time of the MRCA for bornavirus N was estimated to be smaller than 0.3 MYA. These results suggest that the integration time of itEBLN was much later than the loss of LINE-1 activity, supporting the non-LINE-1-mediated Fedratinib mw integration of itEBLN.”
“Carbon tetrachloride (1 ml/kg body weight as a 1:1 mixture of CCl(4) and mineral oil) was orally administered to rats. After 12 h, the activity of plasma ALT (alanine aminotransferase) was significantly higher than that of the control group, and plasma ALT and AST (aspartate aminotransferase) activities significantly

increased 24 h after CCl(4) administration. These results indicated that the necrotic process had initiated at about 12 h and developed thereafter. After 6-24 h of CCl(4) administration, the hepatic level of vitamin C, the most sensitive indicator of oxidative stress, decreased significantly, indicating that oxidative stress was significantly enhanced 6 h after CCl(4) Etomoxir Metabolism inhibitor intoxication and thereafter. Oral administration of vitamin E (1 ml/kg

body weight as a 1:1 mixture of alpha-tocopherol and mineral oil) 12 h before CCl(4) administration caused a significant elevation of liver vitamin E level and ameliorated liver necrosis 24 h after CCl(4) intoxication based on plasma AST and ALT. Vitamin E also significantly restored the hepatic vitamin C concentration 12 and 24 h after CCl(4) intoxication, demonstrating that vitamin E functioned as an antioxidant. The liver vitamin E concentration was not changed by vitamin E supplementation to rats that did not receive CCl(4). This result indicated that vitamin E accumulated in the damaged liver. The activation of JNK, ERK1/2 and p38 MAPK took place 1.5 h after CCl(4) administration. Co-administration of alpha-tocopherol with CCl(4) did not

affect these early changes in MAPKs.”
“Friedreich’s ataxia (FRDA) is an autosomal recessive disease caused by mutations that produce a deficiency in frataxin. Despite the importance of neurodegeneration in FRDA, little is known about the consequences ABT-737 cost of frataxin deficiency in neuronal cells. Here we describe a neuronal cell model for FRDA based on the use of lentiviral vectors that carry minigenes encoding frataxin-specific shRNAs that silence the expression of this gene. These lentivectors can knockdown frataxin expression in human neuroblastoma SH-SY5Y cells, which results in large-scale cell death in differentiated neuron-like cells but not in undifferentiated neuroblastoma cells. Frataxin-deficient neuron-like cells appear to die through apoptosis that is accompanied by up-regulation of p53, PUMA and Bax and activation of caspase-3.

Several works have demonstrated that lithium can either inhibit or stimulate growth of normal and cancer cells. Hence, the present study is focused to analyze the underlying mechanisms that dictate the biphasic oncogenic properties of LiCl. In the current study, we have investigated the dose-dependent SIS3 effects of LiCl on human breast cancer cells (MCF-7) by assessing the consequences on cytotoxicity and protein expressions of signaling molecules crucial for the maintenance of cell survival. The results showed breast cancer cells respond in a diverse manner to LiCl, i.e., at lower concentrations (1, 5, and 10 mM), LiCl induces cell

survival by inhibiting apoptosis through regulation of GSK-3 beta, caspase-2, Bax, and cleaved caspase-7 and by activating anti-apoptotic proteins (Akt, beta-catenin, Bcl-2, and cyclin D1). In contrast, at high concentrations (50 and 100 mM), it induces apoptosis by reversing these effects. Moreover, LiCl also alters the sodium and potassium levels thereby altering the membrane potential of MCF-7 cells. Thus it is inferred that LiCl exerts a dose-dependent biphasic effect on breast cancer cells (MCF-7) by altering the apoptotic/anti-apoptotic balance.”
“Aminopeptidase N (APN/CD13) is one of the essential proteins for tumour invasion, angiogenesis and metastasis as it is over-expressed on the surface of different tumour cells. Based on our previous work that L-isoserine dipeptide derivatives

were potent APN inhibitors, we designed and synthesized L-isoserine tripeptide derivatives as APN inhibitors. Among these compounds, selleck chemicals llc one compound 16l (IC50 = 2.51 +/- 0.2 +/- mu M) showed similar inhibitory effect compared with control compound Bestatin (IC50 = 6.25 +/- 0.4 mu M) and it could be used as novel lead compound for the APN inhibitors development as anticancer agents in the future.”
“The mechanisms governing the development of cardiac pacemaking and conduction system are not well understood. In order to provide evidence for see more the derivation of pacemaking cells and the signal that induce and maintain the cells in the developing heart, Nkx2.5(+) cardiac progenitor cells (CPCs) were isolated from embryonic heart tubes of rats. Endothelin-1 was

subsequently added to the CPCs to induce differentiation of them towards cardiac pacemaking cells. After the treatment, Nkx2.5(+) CPCs displayed spontaneous beating and spontaneously electrical activity as what we have previously described. Furthermore, RT-PCR and immunofluorescence staining demonstrated that Tbx3 expression was increased and Nkx2.5 expression was decreased in the induced cells 4 days after ET-1 treatment. And the significantly increased expression of Hcn4 and connexin-45 were detected in the induced cells 10 days after the treatment. In addition, Nkx2.5(+) CPCs were transfected with pGCsi-Tbx3 4 days after ET-1 treatment in an attempt to determine the transcription regulatory factor governing the differentiation of the cells into cardiac pacemaking cells.

To investigate this genotype-phenotype incongruence of “low-MIC vancomycin-resistant enterococci” (LM-VRE), we examined the molecular characteristics of these isolates, including the presence of the vanB operon, using PCR amplification and DNA sequencing. All LM-VRE isolates contained vanB associated with the transposon Tn1549 and were polyclonal. Sequencing of the vanB ligase gene showed no differences from the prototype vanB2. In addition, we examined supplemented

media to improve phenotypic detection of these isolates. Etest detection of LM-VRE improved when Mueller-Hinton agar (MHA) and brain heart infusion agar (BHIA) were supplemented with 10 g/liter oxgall (MHA-Oxg and BHIA-Oxg, respectively).

We assessed the sensitivity and specificity of these find more media to detect vancomycin resistance using vancomycin-resistant vanB-containing E. faecium (n = 11), vancomycin-susceptible LY2835219 research buy (van negative) E. faecium (n = 11), vancomycin-susceptible (van negative) E. faecalis (n = 11), and our LM-VRE (n = 23) isolates. After 48 h of incubation, both MHA-Oxg and BHIA-Oxg were 100% (34/34) sensitive and 100% (22/22) specific in the identification of vancomycin resistance. These findings suggest that supplementation of MHA or BHIA with 10 g/liter oxgall should be considered in laboratories where VRE detection protocols rely primarily on strain phenotype rather than early vanB gene detection by PCR.”
“Community-associated methicillin-resistant Staphylococcus aureus Liproxstatin-1 chemical structure (CA-MRSA) has recently emerged worldwide. The United States, in particular, is experiencing a serious

epidemic of CA-MRSA that is almost entirely caused by an extraordinarily infectious strain named USA300. However, the molecular determinants underlying the pathogenic success of CA-MRSA are mostly unknown. To gain insight into the evolution of the exceptional potential of USA300 to cause disease, we compared the phylogeny and virulence of USA300 with that of closely related MRSA clones. We discovered that the sublineage from which USA300 evolved is characterized by a phenotype of high virulence that is clearly distinct from other MRSA strains. Namely, USA300 and its progenitor, USA500, had high virulence in animal infection models and the capacity to evade innate host defense mechanisms. Furthermore, our results indicate that increased virulence in the USA300/USA500 sublineage is attributable to differential expression of core genome-encoded virulence determinants, such as phenol-soluble modulins and alpha-toxin. Notably, the fact that the virulence phenotype of USA300 was already established in its progenitor indicates that acquisition of mobile genetic elements has played a limited role in the evolution of USA300 virulence and points to a possibly different role of those elements.

In vitro analysis revealed “that propranolol reduces the expression of HIF-1 alpha in hemangioma cells in a dose- and time-dependent manner, mainly by acting on P2-AR. Interestingly, it was observed that overexpression of HIF-1 alpha apparently abrogated the inhibitory effects GDC-0973 ic50 of propranolol on vascular endothelial growth factor (VEGF) expression and cell growth. Our data further demonstrated that propranolol inhibited the signal transducer and activator of transcription 3 (STAT3), a critical oncogenic signaling molecule,

and the anti-apoptotic protein Bcl-2. Additionally, overexpression of HIF-1 alpha significantly reversed the inhibitory effects of propranolol on STAT3 signaling. In a mouse xenograft hemangioma model, overexpression of HIF-1 alpha significantly attenuated the therapeutic effects of propranolol and inhibited propranolol-induced hemangioma cell apoptosis. Moreover, the protein levels of VEGF, phosphorylated STAT3, total STAT3 and Bcl-2 were significantly upregulated by HIF-1 alpha overexpression in propranolol-treated nude mice bearing hemangiomas. Collectively, our data provide evidence that propranolol may regress infantile hemangiomas by suppressing VEGF and STAT3 signaling pathways in an HIF-1 alpha-dependent manner.”
“The expanding repertoire of genetically encoded

biosensors constructed from variants of Aequorea victoria green fluorescent protein (GFP) enable the imaging of a variety Milciclib clinical trial of intracellular biochemical Ulixertinib processes. To facilitate the imaging

of multiple biosensors in a single cell, we undertook the development of a dimerization-dependent red fluorescent protein (ddRFP) that provides an alternative strategy for biosensor construction. An extensive process of rational engineering and directed protein evolution led to the discovery of a ddRFP with a K-d of 33 mu M and a 10-fold increase in fluorescence upon heterodimer formation. We demonstrate that the dimerization-dependent fluorescence of ddRFP can be used for detection of a protein-protein interaction in vitro, imaging of the reversible Ca2+-dependent association of calmodulin and M13 in live cells, and imaging of caspase-3 activity during apoptosis.”
“Expression of STAT-3/pSTAT3 in colorectal cancer (CRC) patients of Indian origin was studied to assess its significance in early detection and apoptosis regulation. Colorectal tissues with malignant lesions were STAT3/pSTAT3 positive in 66% of the cases and among these positive cases, well differentiated, moderately differentiated and poorly differentiated cancers were 86%, 60% and 0% respectively. All CRC specimens studied were immunoreactive with anti-carcinoembryonic antigen antibody.

The results suggest

that group II mGluRs regulate both fast glutamatergic and GABAergic synaptic transmission in the ICC, probably through a presynaptic mechanism due to reduction of transmitter release. (C) 2010 Elsevier B.V. All rights reserved.”
“Few genes are known to be involved in renal cell carcinoma (RCC) development and progression. The cell-specific transcription factor hepatocyte nuclear factor 4 alpha (HNF4 alpha) is down-regulated in RCC and we have shown that HNF4 alpha inhibits cell proliferation in the embryonic kidney cell line HEK293. To clarify the possible tumor suppressor activity of HNF4 alpha we analyzed the whole human expression profile in HEK293 cells upon HNF4 alpha induction. By comparing Wnt tumor induced and unincluced cells, we identified 1411 differentially expressed genes. Using RNA interference, we screened 56 HNF4 alpha-regulated genes for their possible role in mediating inhibition of cell proliferation triggered by HNF4 alpha. We demonstrate that 14 of these regulated genes are able to contribute to the inhibitory effect of HNF4 alpha on cell proliferation, including well-known cancer genes, such as CDKN1A(p21), TGFA, MME (NEP) and ADAMTS1. In addition, the genes SEPP1, THEM2, BPHL, DSC2,

ANK3, ALDH6A1, EPHX2, NELL2, EFHD1 and PROS1 are also part Ulixertinib datasheet of the network of HNF4 ZD1839 alpha target genes that regulate proliferation in HEK293 cells. Therefore, we postulate that HNF4 alpha orchestrates, at least, these 14 genes to regulate cell proliferation in HEK293 cells and that down-regulation of HNF4 alpha could contribute to the progression of kidney cancer.”
“PURPOSE. Here, we examined the development, composition, and structural organization of the ciliary zonule of the mouse. Fibrillin 1, a large glycoprotein enriched in force-bearing tissues, is a prominent

constituent of the mouse zonule. In humans, mutations in the gene for fibrillin 1 (FBN1) underlie Marfan syndrome (MS), a disorder characterized by lens dislocation and other ocular symptoms.\n\nMETHODS. Fibrillin expression was analyzed by in situ hybridization. The organization of the zonule was visualized using antibodies to Fbn1, Fbn2, and microfibril-associated glycoprotein-1 (Magp1) in conjunction with 5-ethynyl-2′-deoxyuridine (EdU), an S-phase marker.\n\nRESULTS. Microfibrils, enriched in Fbn2 and Magp1, were prominent components of the temporary vascular tunic of the embryonic lens. Fbn2 expression by nonpigmented ciliary epithelial cells diminished postnatally and there was a concomitant increase in Fbn1 expression, especially in cells located in valleys between the ciliary folds. Zonular fibers projected from the posterior pars plicata to the lens in anterior, equatorial, and posterior groupings.

The analysis of the mean lengths of the development of larvae at different temperatures and relative humidity with the 16L:8D showed that the developmental time of larvae decreases with increasing

relative humidity. This factor was significant, while the effect of the increase of temperature and the interaction between the temperature and relative humidity was not significant. At 0L:24D a decrease of the developmental time of larvae was observed when temperature was increased, both at 50 and at 70% RH. The developmental time of pupae was between 4 and 15 days, the shortest mean developmental time with a highest number of alive individuals was observed at 29 +/- MK-0518 research buy 1 degrees C, and 0L:24D, and both levels of relative humidity. The pupal developmental time showed small differences at the two relative

humidities, with the exception of 26 +/- 1 degrees C and 16L:8D at 50 +/- 5 % RH where the mean development time was 10.7 days (+/-1.3 SD), and at 70 +/- 5 % RH with mean duration of 9.1 days (+/-1.6 SD). The photoperiod influenced the length of development in I. inquinato as the shortest mean development periods were observed in the tests carried out with 0L:24D.”
“Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by skeletal muscle atrophy and weakness, ultimately leading to respiratory failure. The purpose of this study was to assess changes in skeletal muscle excitation-contraction (E-C) coupling and intracellular Ca2+ handling during disease progression in the G93A*SOD1 ALS transgenic (ALS Tg) mouse model. To assess E-C coupling, single muscle

selleck inhibitor fibers were electrically stimulated (10-150 Hz), and intracellular free Ca2+ concentration was assessed using fura-2. There were no differences in peak fura-2 ratio at any stimulation frequency at 70 days (early presymptomatic). However, at 90 days (late presymptomatic) and 120-140 days (symptomatic), fura-2 ratio was increased at 10 Hz in ALS Tg compared with wild-type (WT) fibers (0.670 +/- 0.02 vs. 0.585 +/- 0.02 for 120-140 days; P smaller than 0.05). There was also a significant increase in resting fura-2 ratio at 90 days (0.351 +/- 0.008 vs. 0.390 +/- 0.009 in WT vs. ALS Tg; P smaller than 0.05) and 120-140 Apoptosis inhibitor days (0.374 +/- 0.001 vs. 0.415 +/- 0.003 in WT vs. ALS Tg; P smaller than 0.05). These increases in intracellular Ca2+ in ALS Tg muscle were associated with reductions in the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase proteins SERCA1 (to 54% and 19% of WT) and SERCA2 (to 56% and 11% of WT) and parvalbumin (to 80 and 62% of WT) in gastrocnemius muscle at 90 and 120-140 days, respectively. There was no change in dihydropyridine receptor/L-type Ca2+ channel at any age. Overall, these data demonstrate minimal changes in electrically evoked Ca2+ transients but elevations in intracellular Ca2+ attributable to decreased Ca2+-clearance proteins.

Histomorphometric analysis of bone to implant contact (BIC) and bone area was performed at 4 h, 1, 2, 4 and 8 weeks.\n\nWound healing initiated with a coagulum that was substituted by a provisional matrix at 1 week. Bone formation started concomitant to a marked bone resorption. GM6001 mw At

2 weeks, woven bone formation was evident and gradually remodelled into lamellar bone at 4 and 8 weeks. BIC increased similarly throughout the study in both groups with a tendency to higher percentages for the test devices at 2 and 4 weeks. The influence of the DCD nano-particles was more evident at the fourth premolar site.\n\nOsseointegration occurred similarly at both implant groups, although the socket dimension appeared to influence bone healing. It is suggested that the enhanced nano-topography has a limited effect in the immediate implant surgical protocol.”
“Purpose: Improving dose calculation accuracy is crucial in intensity-modulated radiation therapy (IMRT). We have developed a method for generating a phase-space-based dose kernel for IMRT planning of lung cancer patients.\n\nMethods: www.selleckchem.com/products/psi-7977-gs-7977.html Particle transport in the linear accelerator treatment head of a 21EX, 6 MV photon beam (Varian Medical Systems, Palo Alto, CA) was simulated using the EGSnrc/BEAMnrc code system. The phase space information was recorded under the secondary jaws. Each particle in the phase space file was associated with a beamlet whose index was

calculated and saved in the particle’s Apoptosis Compound Library LATCH variable. The DOSXYZnrc code was modified to accumulate the energy deposited by each particle based on its beamlet index. Furthermore, the central axis of each beamlet was calculated from the orientation of all the particles in this beamlet.

A cylinder was then defined around the central axis so that only the energy deposited within the cylinder was counted. A look-up table was established for each cylinder during the tallying process. The efficiency and accuracy of the cylindrical beamlet energy deposition approach was evaluated using a treatment plan developed on a simulated lung phantom.\n\nResults: Profile and percentage depth doses computed in a water phantom for an open, square field size were within 1.5% of measurements. Dose optimized with the cylindrical dose kernel was found to be within 0.6% of that computed with the nontruncated 3D kernel. The cylindrical truncation reduced optimization time by approximately 80%.\n\nConclusions: A method for generating a phase-space-based dose kernel, using a truncated cylinder for scoring dose, in beamlet-based optimization of lung treatment planning was developed and found to be in good agreement with the standard, nontruncated scoring approach. Compared to previous techniques, our method significantly reduces computational time and memory requirements, which may be useful for Monte-Carlo-based 4D IMRT or IMAT treatment planning. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org.

Results showed that optimum growth of the selected Bacillus spp. occurred at 30 degrees C, pH 7.5, and 1.5% NaCl, and they secreted protease, amylase, and lipase. Vibrio spp. were also inhibited by 3 Bacillus spp. In addition, the selected Bacillus spp. had no pathogenic effect on shrimp postlarvae (PL) and were able to reduce TAN. They promoted better AICAR nmr growth and survival in shrimp PL without water exchange. This study was a systematic approach undertaken for the selection of suitable Bacillus

spp. as bioremediators for a Penaeus monodon culture system.”
“The current study investigated the immediate neurophysiological effects of different types of massage in healthy adults using functional magnetic resonance imaging (fMRI). Much attention has been given to the default mode network, a set of brain regions showing greater activity in the resting state. These regions (i.e. insula, posterior and anterior cingulate, inferior parietal and medial prefrontal cortices) have been postulated to be involved in the neural correlates of consciousness, specifically in arousal and

awareness. We posit that massage would modulate these same regions given the benefits and pleasant affective properties of touch. To this end, healthy participants were randomly assigned to one of four conditions: 1. Swedish massage, 2. reflexology, 3. massage with an object or 4. a resting control condition. The right

foot was massaged while each participant performed a cognitive association CA4P Cytoskeletal Signaling inhibitor task in the scanner. We found that the Swedish massage treatment Selleckchem Rabusertib activated the subgenual anterior and retrosplenial/posterior cingulate cortices. This increased blood oxygen level dependent (BOLD) signal was maintained only in the former brain region during performance of the cognitive task. Interestingly, the reflexology massage condition selectively affected the retrosplenial/posterior cingulate in the resting state, whereas massage with the object augmented the BOLD response in this region during the cognitive task performance. These findings should have implications for better understanding how alternative treatments might affect resting state neural activity and could ultimately be important for devising new targets in the management of mood disorders.”
“The recently described novel gyroviruses may infect chickens and/or humans; however, their pathogenic potential is unknown. In our metagenomic investigation, we detected many of the novel gyroviruses in the fecal viromes of ferrets with lymph node and organ enlargement. The complete genomic sequences of selected gyrovirus strains showed 90.7-99.4 % similarity to homologous reference gyrovirus strains.

Syndrome X is associated with endothelial dysfunction, which is a key feature in the evolution of atherosclerosis. We sought to determine whether serum adiponectin levels are decreased in patients with syndrome X.\n\nMethods – Twenty-three syndrome X patients (14 men, 9 women) who presented with stable angina pectoris, had

a positive non-invasive stress test or an abnormal myocardial perfusion scintigraphy single photon emission computed tomography (MPS SPECT) and a normal coronary angiogram, were included in our study, as were 17 asymptomatic PF-562271 purchase healthy subjects (13 men, 4 women) with normal results from non-invasive stress testing. The serum adiponectin levels and lipid profiles of the patients and control subjects were determined with venous samples Cilengitide clinical trial collected after a 12-hour fast. The results were analysed by a Mann Whitney U test.\n\nResults – Mean age (54.1 +/- 11.8

y in patients and 59.8 +/- 9.6 y in control subjects, P>0.05) and body mass index (28.0 +/- 3.3 in patients and 27.1 +/- 4.2 in control subjects, P>0.05) did not differ between the two groups.Adiponectin levels in patients with syndrome X (1.5 +/- 1.1 mu g/dl) were significantly lower than those in the control group (5.3 +/- 2.9 mu g/dl, P < 0.0001). Serum total cholesterol (TCHOL), triglyceride (TG), LDL, and HDL-cholesterol levels did not differ between the two groups (P>0.05).\n\nConclusion – Serum adiponectin levels were lower in patients with syndrome X, and these low adiponectin concentrations may cause endothelial dysfunction. Thus, patients with a marked drop in adiponectin levels may be considered at high risk for future

coronary events and may therefore benefit from additional pharmacological treatment.”
“We aimed to compare the effectiveness of experimental middle hernia defect repair in regard to the transverse and longitudinal positioning of anisotropic lightweight surgical mesh.\n\nThe mechanical properties of fascial layers and surgical mesh DynaMesh(A (R))-PP Light were determined in two Dibutyryl-cAMP perpendicular directions under uniaxial tension. In 12 male Wistar rats, middle hernia defect was repaired by the sublay technique. In six animals, the mesh was positioned across (DLH group) and in the other six along (DLV group) the midline. At 6 months after implantation, mesh deformation, structural rearrangement, and repaired abdominal wall biomechanics were evaluated. Histological sections were stained with van Giesen and Mallory’s trichrome.\n\nThe anisotropic mechanical properties of the mesh and fascial layers coincided in the DLH group, but did not correspond to each other in the DLV group. In the DLV group, meshes were stretched in width by 11.4% and reduced in length by 12.7%. In all animals, the lower edge of the mesh was shifted to a defect area with margin hernia formation in two rats. Constant shear stress caused disproportional connective tissue formation.

8% increase in NEO/PALEO. Our results are consistent with a mechanism in which the regional redistribution MAPK Inhibitor Library of pulmonary blood flow is mediated by local intrapulmonary factors.”
“A field experiment was conducted to investigate the effect of a symbiotic nitrogen fixing bacterium Bradyrhizobium japonicum

strain TAL-102 and a commercial biofertlizer EM (effective microorganisms) on growth, nodulation and yield of soybean [Glycine max (L.) Wilczek] in soils amended either with farmyard manure or Trifolium alexandrinum L. green manure @ 20 tons ha(-1) each. In green manure amendment, B. japonicum inoculation significantly enhanced number and biomass of nodules resulting in a significant increase of 27, 65 and 55% in shoot biomass and number and biomass of pods, respectively.

In farmyard manure amended soil, B. japonicum inoculation significantly enhanced BIX01294 fresh biomass of nodules. As a result a significant increase of 45 and 47% in shoot biomass and number of pods was recorded, respectively. Generally, the effect of sole EM application on various studied parameters was insignificant in both the soil amendment systems. Combined application of EM and B. japonicum in green manure amended soil reduced shoot growth and number of pods as compared to sole B. japonicum inoculation. Conversely, in farmyard manure amendment, plants co-inoculated with B. japonicum and EM exhibited highest and significantly greater shoot biomass, and number and biomass of pods as compared to all other treatments. The present study concludes that soybean yield can be significantly enhanced by the application of B. japonicum and EM www.selleckchem.com/products/sbe-b-cd.html in farmyard manure amendment.”
“Shkryl VM, Maxwell JT, Domeier TL, Blatter LA. Refractoriness of sarcoplasmic reticulum Ca2+ release determines Ca2+ alternans in atrial myocytes. Am J Physiol

Heart Circ Physiol 302: H2310-H2320, 2012. First published March 30, 2012; doi:10.1152/ajpheart.00079.2012.-Cardiac alternans is a recognized risk factor for cardiac arrhythmia and sudden cardiac death. At the cellular level, Ca2+ alternans appears as cytosolic Ca2+ transients of alternating amplitude at regular beating frequency. Cardiac alternans is a multifactorial process but has been linked to disturbances in intracellular Ca2+ regulation. In atrial myocytes, we tested the role of voltage-gated Ca2+ current, sarcoplasmic reticulum (SR) Ca2+ load, and restitution properties of SR Ca2+ release for the occurrence of pacing-induced Ca2+ alternans. Voltage-clamp experiments revealed that peak Ca2+ current was not affected during alternans, and alternans of end-diastolic SR Ca2+ load, evaluated by application of caffeine or measured directly with an intra-SR fluorescent Ca2+ indicator (fluo-5N), were not a requirement for cytosolic Ca2+ alternans.