Effect of ethanol on action potential and ionic membrane currents in rat ventricular myocytes

Bébarová, Markéta; Matejovič, Peter; Pásek, Michal; Ohlídalová, Dana; Jansová, Dagmar; Šimurdová, Milena; Šimurda, Jiří

doi:10.1111/j.1748-1716.2010.02162.x

Cited by 37 publications

(41 citation statements)

References 44 publications

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“…Thus, it seems to be the most suitable solvent to dissolve the hydrophobic compounds in such ells. Ethanol is also used as a solvent for hydrophobic compounds in experimental studies (28). Previous studies demonstrated that ethanol modulates the cell growth and suppresses cell proliferation dose dependently (29).…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic Effects of Some Common Organic Solvents on MCF-7, RAW-264.7 and Human Umbilical Vein Endothelial Cells

Jamalzadeh¹,

Ghafoori²,

Sariri³

et al. 2016

Avicenna J Med Biochem

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Background: Organic solvents are widely used in cell biology experiments. Despite increasing the solubility, they have some moderate toxic effects. Therefore, selecting the appropriate solvent along with the use of suitable concentration insures the accuracy and reliability of experimental results. Objectives: The current study aimed to examine the cytotoxic effects of some organic solvents on various cell models including MCF-7, RAW-264.7 and human umbilical vein endothelial cells (HUVEC). Materials and Methods:To evaluate the cytotoxicity effect of common organic solvents on the MCF-7, RAW-264.7 and HUVEC cells, multi-table tournament (MTT) colorimetric assay, the widely used and validated cytotoxicity test was applied. For this purpose, the selected cells were treated with different concentrations (0, 0.1%, 0.5%, 1%, 1.5%, 2%, 3% and 5% v/v) of four most commonly used organic solvents (acetone, ethanol, dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) and then subjected to MTT experiment. Results: According to the obtained results, the cytotoxicity increased significantly with increasing the concentration of all four solvents compared to that of the control group. Studies with MCF-7, RAW-264.7 and HUVEC suggested that acetone, ethanol and DMSO at concentrations of 0.1% and 0.5%, had little or no toxicity, whereas higher concentrations inhibited the growth of all three cells. Compared with other three solvents, DMF displayed rather greater toxicity. Based on the results, proliferation of MCF-7, RAW-264.7 and HUVEC cells were inhibited by all used organic solvents, dose dependently. Conclusions: Thus, the background experimental error can be reduced remarkably by maximal concentration of 0.5% ethanol, acetone and DMSO and 0.1% DMF in the final treatment medium.

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Section: Discussionmentioning

confidence: 99%

Cytotoxic Effects of Some Common Organic Solvents on MCF-7, RAW-264.7 and Human Umbilical Vein Endothelial Cells

Jamalzadeh¹,

Ghafoori²,

Sariri³

et al. 2016

Avicenna J Med Biochem

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“…In this study, we updated our recently published model of the rat ventricular cardiomyocyte [37] to include characteristics of membrane currents measured in our recent experiments [2,3]. Using this model, we performed simulations allowing to predict the effect of ethanol on AP, SR Ca 2+ load, and intracellular Ca 2+ transient in rat ventricular cells.…”

mentioning

confidence: 97%

“…To obtain at least a rough estimate of the effects of ethanol on AP and Ca 2+ transient in human ventricular cells, we tentatively incorporated the known concentration dependences of ethanol-induced changes in ionic current components evaluated from the available experimental data [2,3,21,36] into a model of the human ventricular cardiomyocyte [13].…”

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confidence: 99%

Acute effects of ethanol on action potential and intracellular Ca2+ transient in cardiac ventricular cells: a simulation study

Pásek

Bébarová

Christé

et al. 2015

Med Biol Eng Comput

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Alcohol consumption may result in electrocardiographic changes and arrhythmias, at least partly due to effects of ethanol on cardiac ionic currents. Contractility and intracellular Ca(2+) dynamics seem to be altered as well. In this study, we integrated the available (mostly animal) experimental data into previously published models of the rat and human ventricular myocytes to assess the share of ionic current components in ethanol-induced changes in AP configuration and cytosolic Ca(2+) transient in ventricular cardiomyocytes. The rat model reproduced well the experimentally observed changes in AP duration (APD) under ethanol (slight prolongation at 0.8 mM and shortening at ≥8 mM). These changes were almost exclusively caused by the ethanol-induced alterations of I K1. The cytosolic Ca(2+) transient decreased gradually with the increasing ethanol concentration as a result of the ethanol-induced inhibition of I Ca. In the human model, ethanol produced a dose-dependent APD lengthening, dominated by ethanol effect on I Kr, the key repolarising current in human ventricles. This effect might contribute to the clinically observed proarrhythmic effects of ethanol in predisposed individuals.

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“…The final tested concentrations were obtained by subsequent dilution in saline solution. The final dose of ethanol was 5m M which was proved not to affect ion currents on the membrane of cardiomyocyte (Bébarová et al 2010).…”

Section: Experimental Groupsmentioning

confidence: 99%

Effect of perphenazine on electrogram of rat isolated heart

et al. 2011

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The aim of this study was to clarify whether administration of antipsychotic perphenazine contributes to the electrophysiological changes of the isolated heart. Fourteen adult male Wistar rats were divided into two groups. Langendorff hearts were perfused with Krebs-Henseleit solution at constant pressure (85 mmHg) and 37 °C (CaCl 2 , 1.2 mM). The electrogram was recorded by touch-free method. The hearts of the first group were exposed to 3.10 -5 M perphenazine, the hearts of the second group to 3.10 -8 M perphenazine. The incidence of arrhythmias and the heart rate and QT interval changes were studied on electrogram during 30 min periods of control, the first perphenazine administration, washout, and the second drug administration.Perphenazine administration significantly prolonged QT (p < 0.001) and QTc (p < 0.05) in group 1. In group 2, QT and QTc prolongation was less pronounced (p < 0.05). A number of arrhythmias appeared, from single premature ventricular complexes to more severe ones in both groups. The heart rate changes were non-significant.We conclude that although phenothiazines are still medicaments of choice in certain psychoses, their cardiovascular side effects should be always taken in consideration. Phenothiazines, Langendorff heart, QT-interval, arrhythmiaCardiovascular system disorders are among the most common causes of morbidity and mortality in developed countries. Many of them are caused by side effects of noncardiovascular drugs whose nature and mode of action vary greatly. A typical example is psychotropic drugs, substances with reported high incidence of cardiovascular side effects, often expressed as various electrophysiological changes. Their representative perphenazine has been used as a psychotropic drug for several decades in therapy of certain psychiatric disorders. It has been reported to induce asymptomatic ECG changes, tachyarrhythmias, self-terminating arrhythmias, or even ventricular fibrillation resulting in the cardiac arrest, especially when overdosed. There are no reports that perphenazine affects electrophysiological properties of the cardiac tissue at therapeutic doses, but, certain ECG changes were observed during its administration in the presence of other potentially arrhythmogenic factors (Magorien et al. 1979).In isolated cardiomyocytes, the effects of perphenazine is functionally related to a variety of ion membrane currents. It reversibly blocks fast sodium current I Na and transient outward potassium current I to . Sensitivity of I Na and I to to perphenazine lies in the micromolar range, whereas the therapeutic plasma concentrations are in the nanomolar range (Bébarová et al. 2009). In isolated rat hearts, perphenazine at concentrations highly above the clinically relevant range caused numerous ECG changes (Langslet 1970).Perphenazine-triggered cardiovascular side effects may be of various severities. Prolonged QT interval is supposed to be a marker for the drug arrhythmogenic capacity. Therefore, L-QT is of major concern; however, there is growing evid...

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Effect of ethanol on action potential and ionic membrane currents in rat ventricular myocytes

Abstract: Our results suggest a slight inhibition of all the currents at ethanol concentrations relevant to deep alcohol intoxication. The concentration dependence measured over a wide range may serve as a guideline when using ethanol as a solvent.

Cited by 37 publications

References 44 publications

Cytotoxic Effects of Some Common Organic Solvents on MCF-7, RAW-264.7 and Human Umbilical Vein Endothelial Cells

Cytotoxic Effects of Some Common Organic Solvents on MCF-7, RAW-264.7 and Human Umbilical Vein Endothelial Cells

Acute effects of ethanol on action potential and intracellular Ca2+ transient in cardiac ventricular cells: a simulation study

Effect of perphenazine on electrogram of rat isolated heart

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