scholarly journals Sarcoplasmic reticulum Ca2+ release is both necessary and sufficient for SK channel activation in ventricular myocytes

2014 ◽  
Vol 306 (5) ◽  
pp. H738-H746 ◽  
Author(s):  
Dmitry Terentyev ◽  
Jennifer A. Rochira ◽  
Radmila Terentyeva ◽  
Karim Roder ◽  
Gideon Koren ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Ventricular Myocytes ◽  
Activation Mechanism ◽  
Sk Channels ◽  
Triggered Activity ◽  
Rat Ventricular Myocytes ◽  
Adult Rat ◽  
Outward Currents ◽  
And Function ◽  
Necessary And Sufficient

SK channels are upregulated in human patients and animal models of heart failure (HF). However, their activation mechanism and function in ventricular myocytes remain poorly understood. We aim to test the hypotheses that activation of SK channels in ventricular myocytes requires Ca2+ release from sarcoplasmic reticulum (SR) and that SK currents contribute to reducing triggered activity. SK2 channels were overexpressed in adult rat ventricular myocytes using adenovirus gene transfer. Simultaneous patch clamp and confocal Ca2+ imaging experiments in SK2-overexpressing cells demonstrated that depolarizations resulted in Ca2+-dependent outward currents sensitive to SK inhibitor apamin. SR Ca2+ release induced by rapid application of 10 mM caffeine evoked repolarizing SK currents, whereas complete depletion of SR Ca2+ content eliminated SK currents in response to depolarizations, despite intact Ca2+ influx through L-type Ca2+ channels. Furthermore, voltage-clamp experiments showed that SK channels can be activated by global spontaneous SR Ca2+ release events Ca2+ waves (SCWs). Current-clamp experiments revealed that SK overexpression reduces the amplitude of delayed afterdepolarizations (DADs) resulting from SCWs and shortens action potential duration. Immunolocalization studies showed that overexpressed SK channels are distributed both at external sarcolemmal membranes and along the Z-lines, resembling the distribution of endogenous SK channels. In summary, SR Ca2+ release is both necessary and sufficient for the activation of SK channels in rat ventricular myocytes. SK currents contribute to repolarization during action potentials and attenuate DADs driven by SCWs. Thus SK upregulation in HF may have an anti-arrhythmic effect by reducing triggered activity.

scholarly journals Role of epicardial mesothelial cells in the modification of phenotype and function of adult rat ventricular myocytes in primary coculture.

1992 ◽  
Vol 71 (1) ◽  
pp. 40-50 ◽  
Author(s):  
H Eid ◽  
D M Larson ◽  
J P Springhorn ◽  
M A Attawia ◽  
R C Nayak ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Mesothelial Cells ◽  
Rat Ventricular Myocytes ◽  
Adult Rat ◽  
And Function

Effects of Mg2+ on Ca2+ waves and Ca2+ transients of rat ventricular myocytes

1996 ◽  
Vol 270 (3) ◽  
pp. H907-H914 ◽  
Author(s):  
H. Terada ◽  
H. Hayashi ◽  
N. Noda ◽  
H. Satoh ◽  
H. Katoh ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Channel Blocker ◽  
Ventricular Myocytes ◽  
Inhibitory Effect ◽  
Antiarrhythmic Action ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Triggered Activity ◽  
Rat Ventricular Myocytes ◽  
High Concentrations

It has been shown that the occurrence of the transient inward current, which is responsible for triggered activity, was often associated with propagating regions of increased intracellular Ca2+ concentration ([Ca2+]i), i.e., the “Ca2+ wave.” To investigate the mechanism of antiarrhythmic action of Mg2+, we have studied effects of high concentrations of Mg2+ on Ca2+ waves in isolated rat ventricular myocytes. [Ca2+]i was estimated using the Ca(2+)-indicating probe indo 1. Ca2+ waves in myocytes, stimulated at 0.2 Hz, were induced by perfusion of isoproterenol (10(-7) M). High Mg2+ concentration suppressed Ca2+ waves in a concentration-dependent manner (36% at 4 mM, 70% at 8 mM, and 82% at 12 mM). The Ca2+ channel blocker verapamil also suppressed Ca2+ waves in a similar way. In contrast with marked depression of Ca2+ transients by verapamil, Ca2+ transients were not affected by high Mg2+ concentration (8 mM). High Mg2+ concentration also reduced frequencies of Ca2+ waves in the absence of electrical stimulation, whereas verapamil failed to reduce frequencies of Ca2+ waves. Reduction in frequency of Ca2+ waves by high Mg2+ concentration was associated with slowing of propagation velocity of Ca2+ waves. To examine whether suppressive effects of high Mg2+ concentration on Ca2+ waves were related to an increase in intracellular Mg2+ concentration ([Mg2+]i), the effect of high-Mg2+ solution on [Mg2+]i was examined in myocytes loaded with mag-fura 2. An increase in extracellular Mg2+ concentration from 1 to 12 mM increased [Mg2+]i from 1.06 +/- 0.16 to 1.87 +/- 0.22 mM (P < 0.01) in 30 min. To examine the effect of high Mg2+ concentration on amount of releasable Ca2+ in the sarcoplasmic reticulum, the effect of high Mg2+ concentration on the Ca2+ transient induced by a rapid application of caffeine was examined. High-Mg2+ solution increased the peak of the caffeine-induced Ca2+ transient. These results suggest that the inhibitory effect of Mg2+ on Ca2+ waves was not due to inhibition of the sarcolemmal Ca2+ channel but could be due to a decreased propensity for the sarcoplasmic reticulum to divest itself of excess Ca2+.

scholarly journals TGF-β1, Released by Myofibroblasts, Differentially Regulates Transcription and Function of Sodium and Potassium Channels in Adult Rat Ventricular Myocytes

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e55391 ◽  
Author(s):  
Kuljeet Kaur ◽  
Manuel Zarzoso ◽  
Daniela Ponce-Balbuena ◽  
Guadalupe Guerrero-Serna ◽  
Luqia Hou ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Ventricular Myocytes ◽  
Rat Ventricular Myocytes ◽  
Adult Rat ◽  
And Function ◽  
Sodium And Potassium ◽  
Tgf Β1

scholarly journals Cardiotrophin-1 induces sarcoplasmic reticulum Ca2+ leak and arrhythmogenesis in adult rat ventricular myocytes

2012 ◽  
Vol 96 (1) ◽  
pp. 81-89 ◽  
Author(s):  
Gema Ruiz-Hurtado ◽  
Nieves Gómez-Hurtado ◽  
María Fernández-Velasco ◽  
Eva Calderón ◽  
Tarik Smani ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Ventricular Myocytes ◽  
Rat Ventricular Myocytes ◽  
Adult Rat

Effect of hypoxia on choline metabolism and phosphatidylcholine biosynthesis in isolated adult rat ventricular myocytes: effects of trifluoperazine

1994 ◽  
Vol 72 (7-8) ◽  
pp. 289-296 ◽  
Author(s):  
Simon W. Rabkin
Keyword(s):  
Myocardial Metabolism ◽  
Ventricular Myocytes ◽  
Choline Uptake ◽  
Rat Ventricular Myocytes ◽  
Adult Rat ◽  
Choline Metabolism ◽  
Phosphatidylcholine Biosynthesis ◽  
Carbonyl Cyanide ◽  
And Function ◽  
Uptake And Metabolism

The purpose of this study was to test the hypothesis that hypoxia alters choline metabolism in adult rat ventricular myocytes and that this is subject to modification by trifluoperazine. Ventricular myocytes were isolated from adult Wistar rats. Choline uptake and metabolism were examined, using [methyl-3H]choline. Choline metabolism to phosphatidylcholine (PC), an important phospholipid for cellular structure and function, was reduced by mild hypoxia while choline uptake was not altered. Trifluoperazine at 10−5 or 10−6 M reduced PC biosynthesis and did not reduce or prevent the effects of hypoxia. Interruption of myocardial metabolism with the combination of carbonyl cyanide m-chlorophenylhydrozone and amobarbital also reduced PC synthesis, although it also reduced choline uptake by the cell. These data indicate that in isolated cardiomyocyte from the adult rat heart that (i) hypoxia impairs PC biosynthesis, (ii) this may be operative in part through inhibition of mitochondrial function, and (iii) trifluoperazine does not act to oppose these effects of hypoxia, but it impairs PC biosynthesis. Thus a component of the membrane phospholipid changes observed with hypoxia may be due to impairment of PC biosynthesis in the cardiomyocyte.Key words: choline uptake, choline metabolism, hypoxia, carbonyl cyanide m-chlorophenylhydrozone, amobarbital, adult rat cardiomyocyte, trifluoperazine.

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