Taurocholate induces changes in rat cardiomyocyte contraction and calcium dynamics

2002 ◽  
Vol 103 (2) ◽  
pp. 191-200 ◽  
Author(s):  
Julia GORELIK ◽  
Sian E. HARDING ◽  
Andrew I. SHEVCHUK ◽  
Duleepa KORALAGE ◽  
Max LAB ◽  
...  
Keyword(s):  
Bile Acid ◽  
Calcium Release ◽  
Contractile Function ◽  
Calcium Transient ◽  
Intrauterine Death ◽  
Ion Conductance ◽  
Rat Cardiomyocytes ◽  
Contraction Amplitude ◽  
Neonatal Cardiomyocytes ◽  
Reduced Rate

Obstetric cholestasis is characterized by raised bile acids, and can be complicated by intrauterine death. We have shown that the bile acid taurocholate causes loss of synchronous beating, bradycardia and cessation of contraction in cultured rat cardiomyocytes [Williamson, Gorelik, Eaton, Lab, de Swiet and Korchev (2001) Clin. Sci. 100, 363–369]. The aim of the present study was to investigate the effect of taurocholate on cardiomyocytes further. We demonstrated a reduced rate of contraction and proportion of beating cells when rat cardiomyocytes were exposed to increasing concentrations of taurocholate (0.1–3.0mM); more marked at higher concentrations (P<0.001). Using scanning ion-conductance microscopy, we also demonstrated reduced amplitude of contraction and calcium transients with taurocholate. Our observations indicate that taurocholate affects calcium release from the sarcoplasmic reticulum and this parallels changes in contractile function. The relationship between the contraction amplitude and calcium transient is not linear, particularly at higher concentrations of taurocholate. We observed different effects in individual cultured neonatal cells; a reversible reduction in rate and amplitude of contraction in some, and irreversible oscillatory (fibrillatory) cessation of beating in others. The effects were more marked with higher concentrations. The contraction amplitude was also reduced in adult cardiomyocytes. The changes were reversible following removal of taurocholate in adult, but not in neonatal, cardiomyocytes exposed to higher concentrations (>0.3mM) (P<0.001). In conclusion we have demonstrated that the bile acid taurocholate can cause different types of dysrhythmia in individual cardiomyocytes. These results provide further support for the hypothesis that obstetric cholestasis may produce cardiac-related sudden intrauterine death.

Intracellular calcium handling heterogeneities in intact guinea pig hearts

2004 ◽  
Vol 286 (2) ◽  
pp. H648-H656 ◽  
Author(s):  
Rodolphe P. Katra ◽  
Etienne Pruvot ◽  
Kenneth R. Laurita
Keyword(s):  
Guinea Pig ◽  
Intracellular Calcium ◽  
Calcium Release ◽  
Optical Mapping ◽  
Contractile Function ◽  
Calcium Transient ◽  
Calcium Transients ◽  
Calcium Handling ◽  
Excitation Light ◽  
Intact Heart

Regional heterogeneities of ventricular repolarizing currents and their role in arrhythmogenesis have received much attention; however, relatively little is known regarding heterogeneities of intracellular calcium handling. Because repolarization properties and contractile function are heterogeneous from base to apex of the intact heart, we hypothesize that calcium handling is also heterogeneous from base to apex. To test this hypothesis, we developed a novel ratiometric optical mapping system capable of measuring calcium fluorescence of indo-1 at two separate wavelengths from 256 sites simultaneously. With the use of intact Langendorff-perfused guinea pig hearts, ratiometric calcium transients were recorded under normal conditions and during administration of known inotropic agents. Ratiometric calcium transients were insensitive to changes in excitation light intensity and fluorescence over time. Under control conditions, calcium transient amplitude near the apex was significantly larger (60%, P < 0.01) compared with the base. In contrast, calcium transient duration was significantly longer (7.5%, P < 0.03) near the base compared with the apex. During isoproterenol (0.05 μM) and verapamil (2.5 μM) administration, ratiometric calcium transients accurately reflected changes in contractile function, and, the direction of base-to-apex heterogeneities remained unchanged compared with control. Ratiometric optical mapping techniques can be used to accurately quantify heterogeneities of calcium handling in the intact heart. Significant heterogeneities of calcium release and sequestration exist from base to apex of the intact heart. These heterogeneities are consistent with base-to-apex heterogeneities of contraction observed in the intact heart and may play a role in arrhythmogenesis under abnormal conditions.

Characterization of positive inotropic effect of colforsin dapropate hydrochloride, a water-soluble forskolin derivative, in isolated adult rat cardiomyocytes

1999 ◽  
Vol 77 (4) ◽  
pp. 225-234 ◽  
Author(s):  
Rikako Miyake ◽  
Hiroyuki Yoshida ◽  
Kouichi Tanonaka ◽  
Yuki Miyamoto ◽  
Hideharu Hayashi ◽  
...  
Keyword(s):  
Calcium Transient ◽  
Water Soluble ◽  
Inotropic Action ◽  
Shortening Velocity ◽  
Adult Rats ◽  
Camp Content ◽  
Rat Cardiomyocytes ◽  
Positive Inotropic Action ◽  
Time To Peak ◽  
Rate Of Increase

The present study was undertaken to characterize the positive inotropic action of colforsin dapropate hydrochloride (NKH477), a novel water-soluble forskolin derivative, on isolated cardiomyocytes of adult rats. Simultaneous measurements of cellular contraction and intracellular calcium concentration ([Ca2+]i) were carried out. The effects of isoprenaline and ouabain on these parameters were also determined for comparison. The contraction and maximum [Ca2+]i of NKH477-, isoprenaline-, or ouabain-treated cells were increased concentration dependently. Peak shortening of NKH477-treated cells was positively correlated with the shortening velocity and inversely with the time to peak shortening. Maximum, but not minimum, [Ca2+]i in NKH477-treated cells was correlated with the rate of increase in [Ca2+]i and inversely with the time to maximum [Ca2+]i. Similar results were obtained with isoprenaline. In contrast, ouabain increased both maximum and minimum [Ca2+]i. Treatment with either NKH477 or isoprenaline increased cellular cAMP content, but treatment with ouabain did not. These results suggest that the positive inotropic action of NKH477 is associated with an increase in [Ca2+]i and acceleration of its kinetics.Key words: adenylate cyclase, calcium transient, colforsin dapropate, isoprenaline, ouabain.

Abstract 124: Function of the Cytoskeletal Proteins Alpha-catenins in Myocardial Growth Control

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Jifen Li ◽  
Sarah Carrante ◽  
Roslyn Yi ◽  
Frans van Roy ◽  
Glenn L. Radice
Keyword(s):  
Heart Development ◽  
Growth Control ◽  
Cytoskeletal Proteins ◽  
Neonatal Rat ◽  
Nuclear Accumulation ◽  
Mouse Heart ◽  
Cardiomyocyte Proliferation ◽  
Rat Cardiomyocytes ◽  
Neonatal Cardiomyocytes

Introduction: Mammalian heart possesses regenerative potential immediately after birth and lost by one week of age. The mechanisms that govern neonatal cardiomyocyte proliferation and regenerative capacity are poorly understood. Recent reports indicate that Yap-Tead transcriptional complex is necessary and sufficient for cardiomyocyte proliferation. During postnatal development, N-cadherin/catenin adhesion complex becomes concentrated at termini of cardiomyocytes facilitating maturation of a specialized intercellular junction structure, the intercalated disc (ICD). This process coincides with the time cardiomyocytes exit cell cycle soon after birth. Hypothesis: We hypothesize that coincident with maturation of ICD α-catenins sequester transcriptional coactivator Yap in cytosol thus preventing activation of genes critical for cardiomyocyte proliferation. Methods: We deleted αE-catenin / αT-catenin genes (α-cat DKO) in perinatal mouse heart and knockdown (KD) α-catenins in neonatal rat cardiomyocytes to study functional impact of α-catenins ablation on ICD maturation. Results: We previously demonstrated that adult α-cat DKO mice exhibited decrease in scar size and improved function post myocardial infarction. In present study, we investigated function of α-catenins during postnatal heart development. We found increase in the number of Yap-positive nuclei (58.7% in DKO vs. 35.8 % in WT, n=13, p<0.001) and PCNA (53.9% in DKO vs. 47.8%, n=8, p<0.05) at postnatal day 1 and day 7 of α-cat DKO heart, respectively. Loss of α-catenins resulted in reduction in N-cadherin at ICD at day 14. We observed an increase number of mononucleated myocytes and decrease number of binucleated myocytes in α-cat DKO compared to controls. Using siRNA KD, we were able to replicate α-cat DKO proliferative phenotype in vitro. The number of BrdU-positive cells was decreased in α-cat KD after interfering with Yap expression (2.91% in α-cat KD vs. 2.02% in α-cat/Yap KD, n>2500 cells, p<0.05), suggesting α-catenins regulate cell proliferation through Yap in neonatal cardiomyocytes. Conclusion: Our results suggest that maturation of ICD regulates α-catenin-Yap interactions in cytosol, thus preventing Yap nuclear accumulation and cardiomyocyte proliferation.

scholarly journals Proinflammatory Cytokines Are Soluble Mediators Linked with Ventricular Arrhythmias and Contractile Dysfunction in a Rat Model of Metabolic Syndrome

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Evaristo Fernández-Sada ◽  
Alejandro Torres-Quintanilla ◽  
Christian Silva-Platas ◽  
Noemí García ◽  
B. Cicero Willis ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Ventricular Arrhythmias ◽  
Mechanical Performance ◽  
Contractile Function ◽  
Ex Vivo ◽  
Heart Function ◽  
Control Group ◽  
Serum Triglycerides ◽  
Rat Cardiomyocytes ◽  
Proinflammatory Mediators

Metabolic syndrome (MS) increases cardiovascular risk and is associated with cardiac dysfunction and arrhythmias, although the precise mechanisms are still under study. Chronic inflammation in MS has emerged as a possible cause of adverse cardiac events. Male Wistar rats fed with 30% sucrose in drinking water and standard chow for 25–27 weeks were compared to a control group. The MS group showed increased weight, visceral fat, blood pressure, and serum triglycerides. The most important increases in serum cytokines included IL-1β(7-fold), TNF-α(84%), IL-6 (41%), and leptin (2-fold), the latter also showing increased gene expression in heart tissue (35-fold). Heart function ex vivo in MS group showed a decreased mechanical performance response to isoproterenol challenge (ISO). Importantly, MS hearts under ISO showed nearly twofold the incidence of ventricular fibrillation. Healthy rat cardiomyocytes exposed to MS group serum displayed impaired contractile function and Ca2+handling during ISO treatment, showing slightly decreased cell shortening and Ca2+transient amplitude (23%), slower cytosolic calcium removal (17%), and more frequent spontaneous Ca2+release events (7.5-fold). As spontaneous Ca2+releases provide a substrate for ventricular arrhythmias, our study highlights the possible role of serum proinflammatory mediators in the development of arrhythmic events during MS.

Caffeine attenuates contraction-induced diminutions of the intracellular calcium transient in mouse lumbrical muscle ex vivo

2019 ◽  
Vol 97 (5) ◽  
pp. 429-435 ◽  
Author(s):  
Ian C. Smith ◽  
Rene Vandenboom ◽  
A. Russell Tupling
Keyword(s):  
Skeletal Muscle ◽  
Intracellular Calcium ◽  
Calcium Release ◽  
Ex Vivo ◽  
Calcium Transient ◽  
Calcium Transients ◽  
Inotropic Effects ◽  
Intracellular Calcium Transient ◽  
Lumbrical Muscle ◽  
Lumbrical Muscles

The amount of calcium released from the sarcoplasmic reticulum in skeletal muscle rapidly declines during repeated twitch contractions. In this study, we test the hypothesis that caffeine can mitigate these contraction-induced declines in calcium release. Lumbrical muscles were isolated from male C57BL/6 mice and loaded with the calcium-sensitive indicator, AM-furaptra. Muscles were then stimulated at 8 Hz for 2.0 s in the presence or absence of 0.5 mM caffeine, at either 30 °C or 37 °C. The amplitude and area of the furaptra-based intracellular calcium transients and force produced during twitch contractions were calculated. For each of these measures, the values for twitch 16 relative to twitch 1 were higher in the presence of caffeine than in the absence of caffeine at both temperatures. We conclude that caffeine can attenuate contraction-induced diminutions of calcium release during repeated twitch contractions, thereby contributing to the inotropic effects of caffeine.

scholarly journals Impaired cellular contractile function in thiamine-deficient rat cardiomyocytes

2009 ◽  
Vol 11 (12) ◽  
pp. 1126-1128 ◽  
Author(s):  
Carolina Rosa Gioda ◽  
Danilo Roman-Campos ◽  
Miguel Araújo Carneiro-Júnior ◽  
Karina Ana da Silva ◽  
Matheus Ornelas de Souza ◽  
...  
Keyword(s):  
Contractile Function ◽  
Rat Cardiomyocytes

scholarly journals Drug Resistant Fetal Arrhythmia in Obstetric Cholestasis

2015 ◽  
Vol 2015 ◽  
pp. 1-4
Author(s):  
Nahide Altug ◽  
Ayse Kirbas ◽  
Korkut Daglar ◽  
Ebru Biberoglu ◽  
Dilek Uygur ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Supraventricular Tachycardia ◽  
Preterm Labor ◽  
Fetal Distress ◽  
Intrauterine Death ◽  
Drug Resistant ◽  
Fetal Arrhythmia ◽  
Antiarrhythmic Treatment

Obstetric cholestasis (OC) is a pregnancy specific liver disease characterized by increased levels of bile acid (BA) and pruritus. Raised maternal BA levels could be associated with intrauterine death, fetal distress, and preterm labor and also alter the rate and rhythm of cardiomyocyte contraction and may cause fetal arrhythmic events. We report a case of drug resistant fetal supraventricular tachycardia and concomitant OC.Conclusion.If there are maternal OC and concomitant fetal arrhythmia, possibility of the resistance to antiarrhythmic treatment should be kept in mind.

Spontaneous and propagated calcium release in isolated cardiac myocytes viewed by confocal microscopy

1992 ◽  
Vol 262 (3) ◽  
pp. C731-C742 ◽  
Author(s):  
D. A. Williams ◽  
L. M. Delbridge ◽  
S. H. Cody ◽  
P. J. Harris ◽  
T. O. Morgan
Keyword(s):  
Confocal Microscopy ◽  
Laser Scanning ◽  
Calcium Release ◽  
Laser Scanning Confocal Microscopy ◽  
Cardiac Cells ◽  
Rat Cardiomyocytes ◽  
Scanning Confocal Microscopy ◽  
Time Period ◽  
Isolated Cardiac Myocytes ◽  
Cell Depolarization

Laser scanning confocal microscopy of the Ca(2+)-sensitive fluorophore fluo-3 has been used to investigate spontaneous and propagated calcium release at high temporal and spatial resolution in enzymatically dispersed rat cardiomyocytes. Waves of fluorescence which propagated throughout the cytosol were evident in spontaneously contracting cardiac cells containing fluo-3, but not in cells containing Ca(2+)-insensitive fluorophores [2',7'-bis (carboxyethyl)-5,6-carboxyfluorescein, SNARF-1, rhodamine-123, or tetramethylrhodamine-labeled dextran]. These waves represent localized areas of elevated [Ca2+] [975 +/- 13 (SE) nM, range 800-1,500 nM; n = 16 cells]. Ca2+ waves were initiated by the spontaneous release of Ca2+ from the sarcoplasmic reticulum (SR) and propagated through cells at rates of 50-150 microns/s. Ca2+ waves were usually initiated at the cell ends, but multiple and variable initiation foci were observed in some cells. Where waves intersected within a single cell there was extinction of wave propagation, confirming the SR as the direct source of Ca2+ and revealing a refractory period in SR Ca2+ release. In some cells high-frequency Ca2+ waves lead to synchronized elevation of [Ca2+] throughout the entire cytosol and within the time period associated with cell depolarization. These observations support the hypothesis that some cardiac arrhythmias are initiated by spontaneous and propagated Ca2+ release and involve subsequent depolarization, global elevation of intracellular [Ca2+], and cell contraction.

scholarly journals Sprint training restores normal contractility in postinfarction rat myocytes

2000 ◽  
Vol 89 (3) ◽  
pp. 1099-1105 ◽  
Author(s):  
Lian-Qin Zhang ◽  
Xue-Qian Zhang ◽  
Timothy I. Musch ◽  
Russell L. Moore ◽  
Joseph Y. Cheung
Keyword(s):  
Contractile Function ◽  
Sprint Training ◽  
Maximal Contraction ◽  
Contraction Amplitude ◽  
Rat Hearts ◽  
Intracellular Ca ◽  
Rat Myocytes ◽  
Time Required ◽  
Cellular Ca ◽  
Homeostatic Mechanisms

The significance of 6–8 wk of high-intensity sprint training (HIST) on contractile abnormalities of myocytes isolated from rat hearts with prior myocardial infarction (MI) was investigated. Compared with the sedentary (Sed) condition, HIST attenuated myocyte hypertrophy observed post-MI primarily by reducing cell lengths but not cell widths. At high extracellular Ca2+ concentration (5 mM) and low pacing frequency (0.1 Hz), conditions that preferentially favored Ca2+ influx over efflux, MI-Sed myocytes shortened less than Sham-Sed myocytes did. HIST significantly improved contraction amplitudes in MI myocytes. Under conditions that favored Ca2+ efflux, i.e., low extracellular Ca2+ concentration (0.6 mM) and high pacing frequency (2 Hz), MI-Sed myocytes contracted more than Sham-Sed myocytes. HIST did not appreciably affect contraction amplitudes of MI myocytes under these conditions. Compared with MI-Sed myocytes, HIST myocytes showed significant improvement in time required to reach one-half maximal contraction amplitude shortening, maximal myocyte shortening and relengthening velocities, and half time of relaxation. Our results indicate that HIST instituted shortly after MI improved cellular contraction in surviving myocytes. Because our previous studies demonstrated that, in post-MI myocytes, HIST improved intracellular Ca2+ dynamics, enhanced sarcoplasmic reticulum Ca2+ uptake and Ca2+ content, and restored Na+/Ca2+ exchange current toward normal, we hypothesized that improvement in MI myocyte contractile function by HIST was likely mediated by normalization of cellular Ca2+ homeostatic mechanisms.

scholarly journals Reversible Notch1 acetylation tunes proliferative signalling in cardiomyocytes

2017 ◽  
Vol 114 (1) ◽  
pp. 103-122 ◽  
Author(s):  
Chiara Collesi ◽  
Giulia Felician ◽  
Ilaria Secco ◽  
Maria Ines Gutierrez ◽  
Elisa Martelletti ◽  
...  
Keyword(s):  
Viral Vector ◽  
Notch Signalling ◽  
Neonatal Rat ◽  
Proliferative Potential ◽  
Cardiomyocyte Proliferation ◽  
Notch Signalling Pathway ◽  
Rat Cardiomyocytes ◽  
Neonatal Cardiomyocytes ◽  
Proliferation And Differentiation ◽  
Acetyltransferase Domain

Abstract Aims The Notch signalling pathway regulates the balance between proliferation and differentiation in several tissues, including the heart. Our previous work has demonstrated that the proliferative potential of neonatal cardiomyocytes relies on Notch1 activity. A deep investigation on the biochemical regulation of the Notch signalling in cardiomyocytes is the focus of the current research. Methods and results We show that the Notch1 intracellular domain is acetylated in proliferating neonatal rat cardiomyocytes and that acetylation tightly controls the amplitude and duration of Notch signalling. We found that acetylation extends the half-life of the protein, and enhanced its transcriptional activity, therefore counteracting apoptosis and sustaining cardiomyocyte proliferation. Sirt1 acted as a negative modulator of Notch1 signalling; its overexpression in cardiomyocytes reverted Notch acetylation and dampened its stability. A constitutively acetylated fusion protein between Notch1 and the acetyltransferase domain of p300 promoted cardiomyocyte proliferation, which was remarkably sustained over time. Viral vector-mediated expression of this protein enhanced heart regeneration after apical resection in neonatal mice. Conclusion These results identify the reversible acetylation of Notch1 as a novel mechanism to modulate its signalling in the heart and tune the proliferative potential of cardiomyocytes.

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