Ionic Mechanisms Underlying the Effects of Vasoactive Intestinal Polypeptide on Canine Atrial Myocardium

Xi, Yutao; Wu, Geru; Ai, Tomohiko; Cheng, Ni; Kališnik, Jurij Matija; Sun, Jia; Abbasi, Shahrzad; Yang, Donghui; Fan, Chenjie; Yuan, Xiaojing; Wang, Suwei; Elayda, MacArthur A.; Gregorič, Igor D.; Kantharia, Bharat K.; Lin, Shien Fong; Cheng, Jie

doi:10.1161/circep.113.000518

Cited by 14 publications

(22 citation statements)

References 56 publications

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“…Action potentials and L-type calcium currents (I Ca,L ) were recorded as per previously published techniques [15]. Whole-cell patch clamp pipettes were pulled from thin-walled borosilicate glass (Harvard Apparatus, March-Hugstetten, Germany) and had resistances between 1 and 3 MΩ when filled with pipette solution.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Substrate Stiffness on Cardiomyocyte Action Potentials

Boothe

Myers

Pok

et al. 2016

Cell Biochem Biophys

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The stiffness of myocardial tissue changes significantly at birth and during neonatal development, concurrent with significant changes in contractile and electrical maturation of cardiomyocytes. Previous studies by our group have shown that cardiomyocytes generate maximum contractile force when cultured on a substrate with a stiffness approximating native cardiac tissue. However, effects of substrate stiffness on the electrophysiology and ion currents in cardiomyocytes have not been fully characterized. In this study, neonatal rat ventricular myocytes were cultured on the surface of flat polyacrylamide hydrogels with elastic moduli ranging from 1 to 25 kPa. Using whole-cell patch clamping, action potentials and L-type calcium currents were recorded. Cardiomyocytes cultured on hydrogels with a 9 kPa elastic modulus, similar to that of native myocardium, had the longest action potential duration. Additionally, the voltage at maximum calcium flux significantly decreased in cardiomyocytes on hydrogels with an elastic modulus higher than 9 kPa, and the mean inactivation voltage decreased with increasing stiffness. Interestingly, the expression of the L-type calcium channel subunit α gene and channel localization did not change with stiffness. Substrate stiffness significantly affects action potential length and calcium flux in cultured neonatal rat cardiomyocytes in a manner that may be unrelated to calcium channel expression. These results may explain functional differences in cardiomyocytes resulting from changes in the elastic modulus of the extracellular matrix, as observed during embryonic development, in ischemic regions of the heart after myocardial infarction, and during dilated cardiomyopathy.

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Section: Methodsmentioning

confidence: 99%

The Effect of Substrate Stiffness on Cardiomyocyte Action Potentials

Boothe

Myers

Pok

et al. 2016

Cell Biochem Biophys

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“…Vasoactive intestinal peptide has also been implicated in the onset of vagally mediated AF 32, 33. Whereas low and moderate levels of vagal nerves stimulation have been shown to be protective in preventing AF, vasoactive intestinal peptide is coreleased with acetylcholine during high‐level vagal nerve stimulation, shortening action potential duration, increasing atrial action potential duration spatial heterogeneity, and causing intra‐atrial conduction block 33, 34. Another potential mechanism behind the elevated risk of AF in the setting of cirrhosis is the elevated levels of galectin‐3 observed in patients with liver disease 35, 36.…”

Section: Discussionmentioning

confidence: 99%

Liver Disease as a Predictor of New‐Onset Atrial Fibrillation

Huang

Dunipace

Sorg

et al. 2018

JAHA

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BackgroundImpact of liver disease on development of atrial fibrillation (AF) is unclear. The purpose of the study was to evaluate prevalence of AF in the setting of liver disease and whether increasing severity of liver disease, using Model for End‐Stage Liver Disease (MELD), is independently associated with increased risk of AF.Methods and ResultsRetrospective data analysis of 1727 patients with liver disease evaluated for liver transplantation between 2006 and 2015 was performed, and patient characteristics were analyzed from billing codes and review of medical records. Multivariable time‐dependent Cox proportional hazards model was performed to determine effect of increasing MELD score on risk of developing AF. Prevalence of AF was 11.2%. Incidence of AF at median follow‐up time of 1.04 years was 8.5%. Both prevalence and incidence of AF increased with increasing MELD scores. Prevalence of AF was 3.7%, 6.4%, 16.7%, and 20.2% corresponding with MELD quartiles 1 to 10, 11 to 20, 21 to 30, and >30, respectively. Compared with patients with MELD quartile 1 to 10, patients with MELD quartile of 11 to 20 had hazard ratio of 2.73 (confidence interval, 1.47–5.07), those in the MELD quartile of 21 to 30 had a hazard ratio of 5.17 (confidence interval, 2.65–10.09), and those with MELD values >30 had hazard ratio of 9.33 (confidence interval, 3.93–22.14) for development of new‐onset AF. Other significant variables associated with new‐onset AF were age, sleep apnea, valvular heart disease, hemodynamic instability, and reduced left ventricular ejection fraction <50% (hazard ratio, of 1.06, 2.17, 3.21, 2.00, and 2.44, respectively).ConclusionsPrevalence and incidence of AF in patients with liver disease is high. Severity of liver disease, as measured by MELD, is an important predictor of new‐onset AF. This novel finding suggests an interaction between inflammatory and neurohormonal changes in liver disease and pathogenesis of AF.

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“…The electrophysiological activity of clusters of iPS-derived beating cells was recorded by an optical mapping system using RH237 a voltage-sensitive dye as previously described [31]. Briefly, beating clusters (22–28 days after differentiation) were cultured in 35 mm dishes overnight, and then surface perfused at 37°C with modified Tyrode’s solution containing 126 mmol/L NaCl, 5.4 mmol/L KCl, 0.8 mmol/L MgCl 2 , 10 mmol/L glucose, and 10 mmol/L HEPES, (pH 7.4 adjusted with 1 mol/L NaOH).…”

Section: Methodsmentioning

confidence: 99%

Generation of electrophysiologically functional cardiomyocytes from mouse induced pluripotent stem cells

Wang

Xi²,

Zheng³

et al. 2016

Stem Cell Research

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Induced pluripotent stem (iPS) cells can efficiently differentiate into the three germ layers similar to those formed by differentiated embryonic stem (ES) cells. This provides a new source of cells in which to establish preclinical allogeneic transplantation models. Our iPS cells were generated from mouse embryonic fibroblasts (MEFs) transfected with the Yamanaka factors, the four transcription factors (Oct4, Sox2, Klf4 and c-Myc), without antibiotic selection or MEF feeders. After formation of embryoid bodies (EB), iPS cells spontaneously differentiated into Flk1-positive cardiac progenitors and cardiomyocytes expressing cardiac-specific markers such as alpha sarcomeric actinin (α-actinin), cardiac alpha myosin heavy chain (α-MHC), cardiac troponin T (cTnT), and connexin 43 (CX43), as well as cardiac transcription factors Nk2 homebox 5 (Nkx2.5) and gata binding protein 4 (gata4). The electrophysiological activity of iPS cell-derived cardiomyocytes (iPS-CMs) was detected in beating cell clusters with optical mapping and RH237 a voltage-sensitive dye, and in single contracting cells with patch-clamp technology. Incompletely differentiated iPS cells formed teratomas when transplanted into a severe combined immunodeficiency (SCID) mouse model of myocardial infarction. Our results show that somatic cells can be reprogrammed into pluripotent stem cells, which in turn spontaneously differentiate into electrophysiologically functional mature cardiomyocytes expressing cardiac-specific makers, and that these cells can potentially be used to repair myocardial infarction (MI) in the future.

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Ionic Mechanisms Underlying the Effects of Vasoactive Intestinal Polypeptide on Canine Atrial Myocardium

Cited by 14 publications

References 56 publications

The Effect of Substrate Stiffness on Cardiomyocyte Action Potentials

The Effect of Substrate Stiffness on Cardiomyocyte Action Potentials

Liver Disease as a Predictor of New‐Onset Atrial Fibrillation

Generation of electrophysiologically functional cardiomyocytes from mouse induced pluripotent stem cells

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