scholarly journals Comparison of contraction and calcium handling between right and left ventricular myocytes from adult mouse heart: a role for repolarization waveform

2006 ◽  
Vol 571 (1) ◽  
pp. 131-146 ◽  
Author(s):  
Richard P. Kondo ◽  
Dorothy A. Dederko ◽  
Christine Teutsch ◽  
Jacqueline Chrast ◽  
Daniele Catalucci ◽  
...  
2016 ◽  
Vol 2 (11) ◽  
pp. e1600844 ◽  
Author(s):  
William C. W. Chen ◽  
Zhouguang Wang ◽  
Maria Azzurra Missinato ◽  
Dae Woo Park ◽  
Daniel Ward Long ◽  
...  

Heart attack is a global health problem that leads to significant morbidity, mortality, and health care burden. Adult human hearts have very limited regenerative capability after injury. However, evolutionarily primitive species generally have higher regenerative capacity than mammals. The extracellular matrix (ECM) may contribute to this difference. Mammalian cardiac ECM may not be optimally inductive for cardiac regeneration because of the fibrotic, instead of regenerative, responses in injured adult mammalian hearts. Given the high regenerative capacity of adult zebrafish hearts, we hypothesize that decellularized zebrafish cardiac ECM (zECM) made from normal or healing hearts can induce mammalian heart regeneration. Using zebrafish and mice as representative species of lower vertebrates and mammals, we show that a single administration of zECM, particularly the healing variety, enables cardiac functional recovery and regeneration of adult mouse heart tissues after acute myocardial infarction. zECM-treated groups exhibit proliferation of the remaining cardiomyocytes and multiple cardiac precursor cell populations and reactivation of ErbB2 expression in cardiomyocytes. Furthermore, zECM exhibits pro-proliferative and chemotactic effects on human cardiac precursor cell populations in vitro. These contribute to the structural preservation and correlate with significantly higher cardiac contractile function, notably less left ventricular dilatation, and substantially more elastic myocardium in zECM-treated hearts than control animals treated with saline or decellularized adult mouse cardiac ECM. Inhibition of ErbB2 activity abrogates beneficial effects of zECM administration, indicating the possible involvement of ErbB2 signaling in zECM-mediated regeneration. This study departs from conventional focuses on mammalian ECM and introduces a new approach for cardiac tissue regeneration.


2013 ◽  
pp. 489-501 ◽  
Author(s):  
M. CAGALINEC ◽  
I. WACZULÍKOVÁ ◽  
O. ULIČNÁ ◽  
D. CHORVAT

Diabetic cardiomyopathy is the leading cause of mortality in type 1 diabetes. Thus study of cardiomyocyte morphology and function during early stages of diabetes using modern analytical methods is of critical importance. Therefore, using confocal microscopy, we determined metric parameters, volumes and contractility, with calcium transients in isolated left-ventricular myocytes at one week after induction of diabetes in rats. Myocyte volume analysis from 3D confocal scans was performed using an automated contour detection algorithm that took the actual shape of the myocytes into account. We showed a significant reduction in myocyte volume in diabetic animals. We also showed a significant reduction in length and width but not in thickness of the myocytes, which suggests disproportional reorganization of the structure of the heart tissue during short-term diabetes. From a functional point of view, we observed a significant decrease in cell shortening at a stimulation frequency of 0.5 Hz. This was accompanied by a decrease in calcium transient amplitude. Together, these data suggest that impaired calcium handling is one of the factors that contributes to the observed decrease in myocyte shortening during early stages of streptozotocin-induced diabetes in rats.


2014 ◽  
Vol 28 ◽  
pp. 29-38 ◽  
Author(s):  
Gayathri Narasimhan ◽  
David Ramiro de Alba-Aguayo ◽  
Ricardo Mondragón-Flores ◽  
Sirenia González-Pozos ◽  
Miyamin J. Miranda-Saturnino ◽  
...  

Polymeric nanoparticles like chitosan nanoparticles may be used to deliver drugs to particular organs, such as heart. However, due to the lack of information about acute effects of chitosan nanoparticles in cardiac calcium handling, we evaluated the same in intact rat left ventricular myocytes. Chitosan nanoparticles were synthesized by ionic gelation method for three different concentrations of chitosan and tripolyphosphate (TPP) such as 1:1, 2:1 and 3:1, respectively. The size of the particles was below 100 nm for the 2:1 and 3:1 chitosan:TPP ratio and 300 nm for 1:1 ratio. The particles synthesized in 3:1 ratio were incubated for 0, 15, 30 and 60 minutes with Fluo-3 loaded cardiomyocytes, their effects were evaluated in local Ca2+ release events using confocal microscopy and compared with control cells. Chitosan nanoparticles increased the amplitude and size of Ca2+ spark by 14.1% and 24.1% at 30 minutes of incubation; while the increment was 24.7% and 28.4% at 60 minutes respectively. Accordingly, rising time of Ca2+ sparks was decreased by 47% at 30 minutes. These changes were reflected in increased local Ca2+ flux by 58.3% and spark-mediated Ca2+ leak by 145.9% and 146.5% at 30, and 60 minutes, respectively. Hence, these results indicate that chitosan nanoparticles modify the properties of local Ca2+ release events mainly at short incubation times and must be taken into account while using these nanoparticles in drug delivery.


2007 ◽  
pp. 275-283 ◽  
Author(s):  
SN Patiyal ◽  
S Sharma

The aim of this study was to analyze the effects of chronic administration of the beta-adrenoceptor agonist clenbuterol (2 mg/kg body weight/day for a period of 30 days) on the major contractile protein (myosin) in the left ventricular muscle of the adult mouse heart. Separation of myosin heavy chain (MHC) isoforms on 7.5 % glycerol SDS-PAGE and subsequent quantification of the gels by laser densitometry showed a 6.5-fold increase in the beta-isoform of MHC in the clenbuterol-treated group. The alpha : beta ratio of these two isoforms in the control group was 98.16+/-0.14 %: 1.83+/-0.14 %, whereas in the treated group it was 88.05+/-1.15 % : 11.95+/-1.15 %. Actomyosin ATPase activity assay demonstrated a significant (20 %) decline in ATPase activity of the tissue in the beta-agonist-treated group. These results suggest that chronic clenbuterol treatment is capable to induced the transformation of MHC isoforms increasing the slow beta-MHC isoform, which may contribute to the altered contractile mechanics of clenbuterol-treated hearts.


Author(s):  
Erik A. Blackwood ◽  
Alina S. Bilal ◽  
Khalid Azizi ◽  
Anup Sarakki ◽  
Christopher C. Glembotski

1997 ◽  
Vol 272 (1) ◽  
pp. H220-H226 ◽  
Author(s):  
M. H. Soonpaa ◽  
L. J. Field

Cardiomyocyte DNA synthesis was examined in normal and injured adult mouse hearts. In preliminary studied DNA synthesis was monitored by [3H]thymidine incorporation, followed by autoradiographic analysis of dispersed cell preparations. No synthetic cells were identified when 20,000 ventricular cardiomyocytes from normal adult hearts were examined. A high throughput assay was developed to establish the actual labeling index for the adult mouse heart. The assay utilized [3H]thymidine incorporation in transgenic mice which expressed a nuclear-localized beta-galactosidase (beta-Gal) reporter gene exclusively in cardiac myocytes. Cardiomyocyte DNA synthesis was evidenced by colocalization of beta-Gal activity and silver grains in autoradiograms of histological sections. Examination of 180,000 ventricular cardiomyocyte nuclei from normal adult transgenic mice identified a single synthetic nucleus, suggesting a maximum labeling index of 0.0005%. Cardiomyocyte DNA synthesis was next examined in hearts injured by focal cauterization of the left ventricular free wall. Only three synthetic nuclei were identified when 36,000 cardiomyocyte nuclei in the perinecrotic zone of the injured heart were examined. No additional synthetic nuclei were identified when 180,000 nuclei in regions distal to the necrotic zone were examined. These data confirm that cardiomyocyte DNA synthesis in the adult mouse heart is extremely rare and provide baseline data for analyses in genetically modified animals.


1999 ◽  
Vol 113 (5) ◽  
pp. 661-678 ◽  
Author(s):  
Haodong Xu ◽  
Weinong Guo ◽  
Jeanne M. Nerbonne

In the experiments here, the time- and voltage-dependent properties of the Ca2+-independent, depolarization-activated K+ currents in adult mouse ventricular myocytes were characterized in detail. In the majority (65 of 72, ≈ 90%) of cells dispersed from the ventricles, analysis of the decay phases of the outward currents revealed three distinct K+ current components: a rapidly inactivating, transient outward K+ current, Ito,f (mean ± SEM τdecay = 85 ± 2 ms); a slowly (mean ± SEM τdecay = 1,162 ± 29 ms) inactivating K+ current, IK,slow; and a non inactivating, steady state current, Iss. In a small subset (7 of 72, ≈ 10%) of cells, Ito,f was absent and a slowly inactivating (mean ± SEM τdecay = 196 ± 7 ms) transient outward current, referred to as Ito,s, was identified; the densities and properties of IK,slow and Iss in Ito,s-expressing cells are indistinguishable from the corresponding currents in cells with Ito,f. Microdissection techniques were used to remove tissue pieces from the left ventricular apex and from the ventricular septum to allow the hypothesis that there are regional differences in Ito,f and Ito,s expression to be tested directly. Electrophysiological recordings revealed that all cells isolated from the apex express Ito,f (n = 35); Ito,s is not detected in these cells (n = 35). In the septum, by contrast, all of the cells express Ito,s (n = 28) and in the majority (22 of 28, 80%) of cells, Ito,f is also present. The density of Ito,f (mean ± SEM at +40 mV = 6.8 ± 0.5 pA/pF, n = 22) in septum cells, however, is significantly (P < 0.001) lower than Ito,f density in cells from the apex (mean ± SEM at +40 mV = 34.6 ± 2.6 pA/pF, n = 35). In addition to differences in inactivation kinetics, Ito,f, Ito,s, and IK,slow display distinct rates of recovery (from inactivation), as well as differential sensitivities to 4-aminopyridine (4-AP), tetraethylammonium (TEA), and Heteropoda toxin-3. IK,slow, for example, is blocked selectively by low (10–50 μM) concentrations of 4-AP and by (≥25 mM) TEA. Although both Ito,f and Ito,s are blocked by high (>100 μM) 4-AP concentrations and are relatively insensitive to TEA, Ito,f is selectively blocked by nanomolar concentrations of Heteropoda toxin-3, and Ito,s (as well as IK,slow and Iss) is unaffected. Iss is partially blocked by high concentrations of 4-AP or TEA. The functional implications of the distinct properties and expression patterns of Ito,f and Ito,s, as well as the likely molecular correlates of these (and the IK,slow and Iss) currents, are discussed.


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