scholarly journals Effect ofα-Allocryptopine on Delayed Afterdepolarizations and Triggered Activities in Mice Cardiomyocytes Treated with Isoproterenol

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Bin Xu ◽  
Yicheng Fu ◽  
Li Liu ◽  
Kun Lin ◽  
Xiaojing Zhao ◽  
...  
Keyword(s):  
Calcium Current ◽  
Ventricular Myocytes ◽  
Treated Group ◽  
Inactivation Kinetics ◽  
Triggered Activity ◽  
Electrophysiological Properties ◽  
Recovery From Inactivation ◽  
Delayed Afterdepolarizations ◽  
Delayed Afterdepolarization ◽  
All Treatment

Objective. To investigate the effect ofα-allocryptopine (ALL) on delayed afterdepolarization (DAD) incidence and triggered activity (TA) in mice administered isoproterenol (ISO).Methods. Mouse ventricular myocytes were isolated. And the cellular electrophysiological properties of ventricular myocytes were investigated.Results. We found that the incidences of DADs and TA in mouse myocytes were increased by ISO treatment. In sharp contrast, triggered arrhythmia events were rarely observed in myocytes with 10 μM ALL treatment. Transient inward current (Iti) was reduced significantly with ALL treatment, which contributed to DAD-related triggered arrhythmia. Compared to Iso-treated group, the L-type calcium current (ICa,L) densities were decreased after exposure to ALL, along with slower activation, quicker inactivation, and longer time constant of recovery from inactivation kinetics.Conclusion. There is less triggered arrhythmia events in ventricular myocytes treated with ALL. This effect may be associated with the inhibition ofItiandICa,L.

Electrophysiological properties of the L-type Ca2+ current in cardiomyocytes from bluefin tuna and Pacific mackerel

2004 ◽  
Vol 286 (4) ◽  
pp. R659-R668 ◽  
Author(s):  
H. A. Shiels ◽  
J. M. Blank ◽  
A. P. Farrell ◽  
B. A. Block
Keyword(s):  
Ventricular Myocytes ◽  
Bluefin Tuna ◽  
Cardiac Performance ◽  
Inactivation Kinetics ◽  
Atrial Myocytes ◽  
Thunnus Orientalis ◽  
Electrophysiological Properties ◽  
The Pacific ◽  
High Maximum ◽  
Pacific Mackerel

Tunas are capable of exceptionally high maximum metabolic rates; such capability requires rapid delivery of oxygen and metabolic substrate to the tissues. This requirement is met, in part, by exceptionally high maximum cardiac outputs, opening the possibility that myocardial Ca2+ delivery is enhanced in myocytes from tuna compared with those from other fish. In this study, we investigated the electrophysiological properties of the cardiac L-type Ca2+ channel current ( ICa) to test the hypothesis that Ca2+ influx would be larger and have faster kinetics in cardiomyocytes from Pacific bluefin tuna ( Thunnus orientalis) than in those from its sister taxon, the Pacific mackerel ( Scomber japonicus). In accordance with this hypothesis, ICa in atrial myocytes from bluefin tuna had significantly greater peak current amplitudes and faster fast inactivation kinetics (-4.4 ± 0.2 pA/pF and 25.9 ± 1.6 ms, respectively) than those from mackerel (-2.7 ± 0.5 pA/pF and 32.3 ± 3.8 ms, respectively). Steady-state activation, inactivation, and recovery from inactivation were also faster in atrial myocytes from tuna than from mackerel. In ventricular myocytes, current amplitude and activation and inactivation rates were similar in both species but elevated compared with those of other teleosts (Vornanen M. Am J Physiol Regul Integr Comp Physiol 272: R1432-R1440, 1997). These results indicate enhanced ICa in atrial myocytes from bluefin tuna compared with Pacific mackerel; this enhanced ICa may be associated with elevated cardiac performance, because ICa delivers the majority of Ca2+ involved in excitation-contraction coupling in most fish hearts. Similarly, ICa is enhanced in the ventricle of both species compared with other teleosts and may play a role in the robust cardiac performance of fishes of the family Scombridae.

ATP promotes development of afterdepolarizations and triggered activity in cardiac myocytes

1994 ◽  
Vol 267 (5) ◽  
pp. H2005-H2011 ◽  
Author(s):  
Y. Song ◽  
L. Belardinelli
Keyword(s):  
Action Potentials ◽  
Ventricular Myocytes ◽  
Extracellular Atp ◽  
Extracellular Medium ◽  
Triggered Activity ◽  
Arrhythmogenic Effect ◽  
Early Afterdepolarization ◽  
Triggered Arrhythmias ◽  
Delayed Afterdepolarization ◽  
Isolated Ventricular Myocytes

The effect of extracellular ATP on transient inward current (Iti), delayed afterdepolarization (DAD), early afterdepolarization (EAD), and triggered activity were investigated in guinea pig isolated ventricular myocytes. ATP alone did not induce afterdepolarizations nor did it significantly alter the resting membrane potentials and action potentials. However, when it was applied with drugs known to increase intracellular Ca2+, ATP facilitated the induction of afterdepolarizations and triggered activity in approximately 60% of the cells. In the presence of isoproterenol, ATP increased the amplitude of Iti and DADs by 55 and 206%, respectively, and caused increases in the amplitude of L-type Ca2+ current (ICa) and EADs, which occasionally led to triggered activity. Similarly, addition of ATP increased the amplitude of Iti and DADs induced by elevated extracellular Ca2+ by 110 and 83%, respectively. Ryanodine inhibited the ATP-induced increase in Iti but not the increase in ICa. In the presence of BAY K 8644 or quinidine, ATP not only further prolonged the action potential durations by 18 +/- 4 and 17 +/- 4%, respectively, but also increased the amplitude of EADs. The present results show a novel arrhythmogenic effect of extracellular ATP, which facilitates the genesis of triggered arrhythmias when Ca2+ influx is increased, probably by further increasing Ca2+ influx from extracellular medium and Ca2+ release from intracellular stores.

Phenotypic differences in transient outward K+ current of human and canine ventricular myocytes: insights into molecular composition of ventricular Ito

2004 ◽  
Vol 286 (2) ◽  
pp. H602-H609 ◽  
Author(s):  
Fadi G. Akar ◽  
Richard C. Wu ◽  
Isabelle Deschenes ◽  
Antonis A. Armoundas ◽  
Valentino Piacentino ◽  
...  
Keyword(s):  
Time Course ◽  
Ventricular Myocytes ◽  
Phenotypic Expression ◽  
Functional Expression ◽  
K Channel ◽  
Inactivation Kinetics ◽  
Phenotypic Properties ◽  
Interacting Protein ◽  
Phenotypic Differences ◽  
Recovery From Inactivation

The Ca2+-independent transient outward K+ current ( Ito) plays an important electrophysiological role in normal and diseased hearts. However, its contribution to ventricular repolarization remains controversial because of differences in its phenotypic expression and function across species. The dog, a frequently used model of human cardiac disease, exhibits altered functional expression of Ito. To better understand the relevance of electrical remodeling in dogs to humans, we studied the phenotypic differences in ventricular Ito of both species with electrophysiological, pharmacological, and protein-chemical techniques. Several notable distinctions were elucidated, including slower current decay, more rapid recovery from inactivation, and a depolarizing shift of steady-state inactivation in human vs. canine Ito. Whereas recovery from inactivation of human Ito followed a monoexponential time course, canine Ito recovered with biexponential kinetics. Pharmacological sensitivity to flecainide was markedly greater in human than canine Ito, and exposure to oxidative stress did not alter the inactivation kinetics of Ito in either species. Western blot analysis revealed immunoreactive bands specific for Kv4.3, Kv1.4, and Kv channel-interacting protein (KChIP)2 in dog and human, but with notable differences in band sizes across species. We report for the first time major variations in phenotypic properties of human and canine ventricular Ito despite the presence of the same subunit proteins in both species. These data suggest that differences in electrophysiological and pharmacological properties of Ito between humans and dogs are not caused by differential expression of the K channel subunit genes thought to encode Ito, but rather may arise from differences in molecular structure and/or posttranslational modification of these subunits.

scholarly journals Long-QT founder variant T309I-Kv7.1 with dominant negative pattern may predispose delayed afterdepolarizations under β-adrenergic stimulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iva Synková ◽  
Markéta Bébarová ◽  
Irena Andršová ◽  
Larisa Chmelikova ◽  
Olga Švecová ◽  
...  
Keyword(s):  
Calcium Current ◽  
Cell Model ◽  
Dominant Negative ◽  
Qtc Interval ◽  
Adrenergic Stimulation ◽  
Patch Clamp Technique ◽  
Long Qt ◽  
Channel Trafficking ◽  
Whole Cell Patch Clamp ◽  
Delayed Afterdepolarizations

AbstractThe variant c.926C > T (p.T309I) in KCNQ1 gene was identified in 10 putatively unrelated Czech families with long QT syndrome (LQTS). Mutation carriers (24 heterozygous individuals) were more symptomatic compared to their non-affected relatives (17 individuals). The carriers showed a mild LQTS phenotype including a longer QTc interval at rest (466 ± 24 ms vs. 418 ± 20 ms) and after exercise (508 ± 32 ms vs. 417 ± 24 ms), 4 syncopes and 2 aborted cardiac arrests. The same haplotype associated with the c.926C > T variant was identified in all probands. Using the whole cell patch clamp technique and confocal microscopy, a complete loss of channel function was revealed in the homozygous setting, caused by an impaired channel trafficking. Dominant negativity with preserved reactivity to β-adrenergic stimulation was apparent in the heterozygous setting. In simulations on a human ventricular cell model, the dysfunction resulted in delayed afterdepolarizations (DADs) and premature action potentials under β-adrenergic stimulation that could be prevented by a slight inhibition of calcium current. We conclude that the KCNQ1 variant c.926C > T is the first identified LQTS-related founder mutation in Central Europe. The dominant negative channel dysfunction may lead to DADs under β-adrenergic stimulation. Inhibition of calcium current could be possible therapeutic strategy in LQTS1 patients refractory to β-blocker therapy.

scholarly journals Synchronization of Spontaneous Calcium Release Waves Among Myocytes in Intact Heart Determines the Magnitude of Delayed Afterdepolarizations and Triggered Activity

2010 ◽  
Vol 98 (3) ◽  
pp. 104a
Author(s):  
J. Andrew Wasserstrom ◽  
Yohannes Shiferaw ◽  
Satvik Ramakrishna ◽  
Heetabh Patel ◽  
Matthew J. O'Toole ◽  
...  
Keyword(s):  
Calcium Release ◽  
Triggered Activity ◽  
Delayed Afterdepolarizations ◽  
Intact Heart

scholarly journals Glycolytic inhibition causes spontaneous ventricular fibrillation in aged hearts

2011 ◽  
Vol 301 (1) ◽  
pp. H180-H191 ◽  
Author(s):  
Norishige Morita ◽  
Jong-Hwan Lee ◽  
Aneesh Bapat ◽  
Michael C. Fishbein ◽  
William J. Mandel ◽  
...  
Keyword(s):  
Ventricular Fibrillation ◽  
Connexin 43 ◽  
Left Ventricular ◽  
Triggered Activity ◽  
Adult Rat ◽  
Rat Hearts ◽  
Intracellular Calcium Ion ◽  
Dependent Protein ◽  
Isolated Cardiac Myocytes ◽  
Delayed Afterdepolarizations

Selective glycolytic inhibition (GI) promotes electromechanical alternans and triggered beats in isolated cardiac myocytes. We sought to determine whether GI promotes triggered activity by early afterdepolarization (EAD) or delayed afterdepolarizations in intact hearts isolated from adult and aged rats. Dual voltage and intracellular calcium ion (Cai2+) fluorescent optical maps and single cell glass microelectrode recordings were made from the left ventricular (LV) epicardium of isolated Langendorff-perfused adult (∼4 mo) and aged (∼24 mo) rat hearts. GI was induced by replacing glucose with 10 mM pyruvate in oxygenated Tyrode's. Within 20 min, GI slowed Cai2+ transient decline rate and shortened action potential duration in both groups. These changes were associated with ventricular fibrillation (VF) in the aged hearts (64 out of 66) but not in adult hearts (0 out of 18; P < 0.001). VF was preceded by a transient period of focal ventricular tachycardia caused by EAD-mediated triggered activity leading to VF within seconds. The VF was suppressed by the ATP-sensitive K (KATP) channel blocker glibenclamide (1 μM) but not (0 out of 7) by mitochondrial KATP block. The Ca-calmodulin-dependent protein kinase II (CaMKII) blocker KN-93 (1 μM) prevented GI-mediated VF ( P < 0.05). Block of Na-Ca exchanger (NCX) by SEA0400 (2 μM) prevented GI-mediated VF (3 out of 6), provided significant bradycardia did not occur. Aged hearts had significantly greater LV fibrosis and reduced connexin 43 than adult hearts ( P < 0.05). We conclude that in aged fibrotic unlike in adult rat hearts, GI promotes EADs, triggered activity, and VF by activation of KATP channels CaMKII and NCX.

Characterization of a TTX-sensitive Na+ current in pacemaker cells isolated from rabbit sinoatrial node

1996 ◽  
Vol 270 (6) ◽  
pp. H2108-H2119 ◽  
Author(s):  
H. Muramatsu ◽  
A. R. Zou ◽  
G. A. Berkowitz ◽  
R. D. Nathan
Keyword(s):  
Action Potential ◽  
Ventricular Myocytes ◽  
Pacemaker Cells ◽  
Na Current ◽  
Recovery From Inactivation ◽  
Cell Recording ◽  
Rabbit Sinoatrial Node ◽  
Best Fit ◽  
Maximum Conductance

A tetrodotoxin (TTX)-sensitive Na+ current (iNa) was investigated in single pacemaker cells after 1-4 days in culture. Ruptured-patch and perforated-patch whole cell recording techniques were used to record iNa and spontaneous electrical activity, respectively. For seven cells exposed to 20 mM Na+ (22-24 degrees C) and held at -98 mV (25% of the channels inactivated), the uncorrected maximum iNa was -39 +/- 10 pA/pF at -29.1 +/- 2.4 (SE) mV, maximum conductance was 0.9 +/- 0.2 nS/pF (1.6 +/- 0.2 mS/cm2). Half-activation and inactivation potentials were -41.4 +/- 2.0 and -90.6 +/- 2.5 mV, and the corresponding slope factors were 6.0 +/- 0.4 and 6.4 +/- 0.6 mV. Inactivation and recovery from inactivation were best fit by sums of two exponentials. During action potential clamp, a TTX-sensitive compensation current accounted for 55% of the upstroke velocity. The results suggest that iNa contributes significantly to the action potential in some nodal pacemaker cells, and the characteristics of iNa are similar to those of atrial and ventricular myocytes.

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