scholarly journals Aminophylline affects the cardiac rat inward rectifier potassium current in a dual way

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
NJD Ramalho ◽  
O Svecova ◽  
R Kula ◽  
M Simurdova ◽  
J Simurda ◽  
...  
Keyword(s):  
Steady State ◽  
Potassium Current ◽  
Ventricular Myocytes ◽  
Inward Rectifier ◽  
Public Institution ◽  
Patch Clamp Technique ◽  
Rat Ventricular Myocytes ◽  
Funding Sources ◽  
Inward Rectifier Potassium Current ◽  
Isolated Rat

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Ministry of Education, Youth and Sports of the Czech Republic Introduction Aminophylline, a bronchodilator used in clinical practice to treat namely severe astma attacks, often induces atrial fibrillation in patients. Modifications of the inward rectifier potassium current IK1 are known to play a role in the genesis of fibrillation. Purpose We aimed to investigate the effect of aminophylline at clinically-relevant concentrations between 3 and 100 µM on IK1 in isolated rat ventricular myocytes. Methods Experiments were performed by the whole cell patch clamp technique on enzymatically isolated rat right ventricular myocytes at room temperature. IK1 was measured as the current sensitive to 100 µM Ba2+. Results We observed a dual steady-state effect of aminophylline at most of the applied concentrations. Either inhibition or activation was apparent in individual cells during application of aminophylline at a given concentration. The smaller was magnitude of the control IK1, the more likely was activation of the current in the presence of aminophylline and vice versa (tested at 10 and 30 µM). The effect was voltage-independent and fully reversible during the subsequent wash-out. The mean aminophylline effect was inhibitory at all concentrations (10, 15, 4, and 23%-inhibition at -50 mV at 3, 10, 30, and 100 µM, respectively). Using a modified version of the population model of IK1 channels that we published before, the dual effect can be explained by interaction of aminophylline with two channel populations in a different way, the first one being inhibited and the second one being activated by the drug. Considering various fractions of these two channel populations in individual cells, varying effects observed in the measured cells can be simulated. Conclusions Aminophylline at clinically-relevant concentrations affects IK1 in rat ventricular myocytes in a dual way, showing both the steady-state activation and inhibition in various cells, even at the same concentration. It may be related to a different effect of the drug on various Kir2.x subunits forming the heterotetrameric IK1 channels present at the cell membrane of a single cell.

Effects of anandamide on potassium channels in rat ventricular myocytes: a suppression of Ito and augmentation of KATP channels

2012 ◽  
Vol 302 (6) ◽  
pp. C924-C930 ◽  
Author(s):  
Qian Li ◽  
Hui-Jie Ma ◽  
Sheng-Li Song ◽  
Min Shi ◽  
Hui-Juan Ma ◽  
...  
Keyword(s):  
Steady State ◽  
Receptor Antagonist ◽  
Potassium Current ◽  
Ventricular Myocytes ◽  
Dependent Manner ◽  
Patch Clamp Technique ◽  
Concentration Dependent Manner ◽  
Inactivation Curve ◽  
Rat Ventricular Myocytes ◽  
Outward Potassium Current

Anandamide is an endocannabinoid that has antiarrhythmic effects through inhibition of L-type Ca2+ channels in cardiomyocytes. In this study, we investigated the electrophysiological effects of anandamide on K+ channels in rat ventricular myocytes. Whole cell patch-clamp technique was used to record K+ currents, including transient outward potassium current ( Ito), steady-state outward potassium current ( Iss), inward rectifier potassium current ( IK1), and ATP-sensitive potassium current ( IKATP) in isolated rat cardiac ventricular myocytes. Anandamide decreased Ito while increasing IKATP in a concentration-dependent manner but had no effect on Iss and IK1 in isolated ventricular myocytes. Furthermore, anandamide shifted steady-state inactivation curve of Ito to the left and shifted the recovery curve of Ito to the right. However, neither cannabinoid 1 (CB1) receptor antagonist AM251 nor CB2 receptor antagonist AM630 eliminated the inhibitory effect of anandamide on Ito. In addition, blockade of CB2 receptors, but not CB1 receptors, eliminated the augmentation effect of anandamide on IKATP. These data suggest that anandamide suppresses Ito through a non-CB1 and non-CB2 receptor-mediated pathway while augmenting IKATP through CB2 receptors in ventricular myocytes.

scholarly journals Acetaldehyde at Clinically Relevant Concentrations Inhibits Inward Rectifier Potassium Current IK1 in Rat Ventricular Myocytes

2015 ◽  
pp. 939-943 ◽  
Author(s):  
M. BÉBAROVÁ ◽  
P. MATEJOVIČ ◽  
M. ŠIMURDOVÁ ◽  
J. ŠIMURDA
Keyword(s):  
Potassium Current ◽  
Cardiac Electrophysiology ◽  
Ventricular Myocytes ◽  
Genetic Defect ◽  
Inward Rectifier ◽  
Significant Inhibition ◽  
Primary Metabolite ◽  
Rat Ventricular Myocytes ◽  
Inward Rectifier Potassium Current ◽  
Acetaldehyde Level

Considering the effects of alcohol on cardiac electrical behavior as well as the important role of the inward rectifier potassium current IK1 in arrhythmogenesis, this study was aimed at the effect of acetaldehyde, the primary metabolite of ethanol, on IK1 in rat ventricular myocytes. Acetaldehyde induced a reversible inhibition of IK1 with IC50 = 53.7±7.7 µM at –110 mV; a significant inhibition was documented even at clinically-relevant concentrations (at 3 µM by 13.1±3.0 %). The inhibition was voltage-independent at physiological voltages above –90 mV. The IK1 changes under acetaldehyde may contribute to alcohol-induced alterations of cardiac electrophysiology, especially in individuals with a genetic defect of aldehyde dehydrogenase where the acetaldehyde level may be elevated.

scholarly journals Effect of acidosis on transient outward potassium current in isolated rat ventricular myocytes

2000 ◽  
Vol 278 (1) ◽  
pp. H50-H59 ◽  
Author(s):  
J. T. Hulme ◽  
C. H. Orchard
Keyword(s):  
Potassium Current ◽  
Voltage Dependence ◽  
Ventricular Myocytes ◽  
Solution Ph ◽  
Patch Clamp Technique ◽  
Inactivation Curve ◽  
Rat Ventricular Myocytes ◽  
Steady State Inactivation ◽  
Perforated Patch Clamp ◽  
Outward Potassium Current

The effect of acidosis on the transient outward K+ current ( Ito ) of rat ventricular myocytes has been investigated using the perforated patch-clamp technique. When the holding potential was −80 mV, depolarizing pulses to potentials positive to −20 mV activated Ito in subepicardial cells but activated little Ito in subendocardial cells. Exposure to an acid solution (pH 6.5) had no significant effect on Ito activated from this holding potential in either subepicardial or subendocardial cells. When the holding potential was −40 mV, acidosis significantly increased Ito at potentials positive to −20 mV in subepicardial cells but had little effect on Ito in subendocardial cells. The increase in Ito in subepicardial cells was inhibited by 10 mM 4-aminopyridine. In subepicardial cells, acidosis caused a +8.57-mV shift in the steady-state inactivation curve. It is concluded that in subepicardial rat ventricular myocytes acidosis increases the amplitude of Ito as a consequence of a depolarizing shift in the voltage dependence of inactivation.

Changes of action potential and L-type calcium channel current of Sprague–Dawley rat ventricular myocytes by different amlodipine isomers

2008 ◽  
Vol 86 (9) ◽  
pp. 620-625 ◽  
Author(s):  
Ru-xing Wang ◽  
Wen-ping Jiang
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Calcium Channel ◽  
Ventricular Myocytes ◽  
Channel Blockers ◽  
Sprague Dawley ◽  
Patch Clamp Technique ◽  
Rat Ventricular Myocytes ◽  
Channel Current ◽  
Steady State Inactivation

To investigate the effects of S- and R-amlodipine (Aml) on action potential (AP) and L-type calcium channel current (ICa-L), the whole-cell patch-clamp technique was used on rat ventricular myocytes to record AP, ICa-L, peak currents, steady-state activation currents, steady-state inactivation currents, and recovery currents from inactivation with S-Aml and R-Aml at various concentrations. Increasing concentrations of S-Aml gradually shortened AP durations (APDs). At concentrations of 0.1, 0.5, 1, 5, and 10 μmol/L, S-Aml blocked 1.5% ± 0.2%, 25.4% ± 5.3%, 65.2% ± 7.3%, 78.4% ± 8.1%, and 94.2% ± 5.0% of ICa-L, respectively (p < 0.05), and the half-inhibited concentration was 0.62 ± 0.12 µmol/L. Current–voltage curves were shifted upward; steady-state activation and inactivation curves were shifted to the left. At these concentrations of S-Aml, the half-activation voltages were –16.01 ± 1.65, –17.61 ± 1.60, –20.17 ± 1.46, –21.87 ± 1.69, and –24.09 ± 1.87 mV, respectively, and the slope factors were increased (p < 0.05). The half-inactivation voltages were –27.16 ± 4.48, –28.69 ± 4.52, –31.19 ± 4.17, –32.63 ± 4.34, and –35.16 ± 4.46 mV, respectively, and the slope factors were increased (p < 0.05). The recovery times from inactivation of S-Aml were prolonged (p < 0.05). In contrast, R-Aml had no effect on AP and ICa-L (p > 0.05) at the concentrations tested. Thus, only S-Aml has calcium channel blockade activity, whereas R-Aml has none of the pharmacologic actions associated with calcium channel blockers.

Ionic Mechanisms Mediating the Differential Effects of Methohexital and Thiopental on Action Potential Duration in Guinea Pig and Rabbit Isolated Ventricular Myocytes 

1999 ◽  
Vol 90 (1) ◽  
pp. 156-164 ◽  
Author(s):  
Anatoly E. Martynyuk ◽  
Timothy E. Morey ◽  
Pekka M.J. Raatikainen ◽  
Christoph N. Seubert ◽  
Donn M. Dennis
Keyword(s):  
Guinea Pig ◽  
Potassium Current ◽  
Ventricular Myocytes ◽  
Inward Rectifier ◽  
Delayed Rectifier ◽  
Delayed Rectifier Potassium Current ◽  
Ionic Mechanisms ◽  
Inward Rectifier Potassium Current ◽  
Calcium Inward Current ◽  
Outward Potassium Current

Background Commonly used barbiturate anesthetics may significantly influence cardiac electrophysiologic characteristics. The authors evaluated thiopental (a thiobarbiturate) and methohexital (an oxybarbiturate), two compounds with similar physicochemical properties but different structures, to determine whether they have distinct effects on the major ionic currents that determine action potential duration (APD) in ventricular myocytes. Methods The effects of thiopental and methohexital (50 microM) on APD at 50% (APD50) and 90% (APD90) repolarization were studied in guinea pig and rabbit single ventricular myocytes using the patch-clamp technique in a whole-cell configuration. The ionic mechanisms underlying the APD changes were evaluated by measuring the anesthetics' effects on the L-type calcium inward current, the inward rectifier potassium current, and the delayed rectifier potassium current in guinea pig cells and on the transient outward potassium current in rabbit cells. Results Thiopental and methohexital caused opposite effects on APD. Whereas thiopental prolonged APD50 and APD90 in guinea pig and rabbit ventricular myocytes, methohexital shortened them. Thiopental markedly depressed both the inward and outward components of the inward rectifier potassium current, whereas methohexital caused minimal inhibition of the inward component and no change in the outward component. The delayed rectifier potassium current was inhibited by thiopental but significantly potentiated by methohexital. Neither thiopental nor methohexital significantly affected the transient outward potassium current or the L-type calcium inward current. Conclusions Despite their similar lipid solubilities, molecular weights, and pKa values, thiopental increased and methohexital decreased the APD in ventricular myocytes by predominantly inhibiting the inward rectifier potassium current and the delayed rectifier potassium current and by increasing the delayed rectifier potassium current, respectively. These characteristics suggest distinct structure-specific actions of barbiturates on the function of myocardial ionic channels.

Zacopride Exerts an Antiarrhythmic Effect by Specifically Stimulating the Cardiac Inward Rectifier Potassium Current in Rabbits: Exploration of a New Antiarrhythmic Strategy

2020 ◽  
Vol 26 (44) ◽  
pp. 5746-5754
Author(s):  
Yuanyuan Lin ◽  
Junhu Li ◽  
Baozhong Zhu ◽  
Qinghua Liu ◽  
Xiaojie Bai ◽  
...  
Keyword(s):  
Potassium Current ◽  
Inward Rectifier ◽  
Antiarrhythmic Effect ◽  
Delayed Rectifier ◽  
Dependent Manner ◽  
Patch Clamp Technique ◽  
Inward Rectifier Potassium Current ◽  
Antiarrhythmic Effects

Background: Zacopride, a potent antagonist of 5-HT3 receptors and an agonist of 5-HT4 receptors, is a gastrointestinal prokinetic agent. In a previous study, we discovered that zacopride selectively stimulated the inward rectifier potassium current (IK1) in the rat and that agonizing IK1 prevented or eliminated aconitine-induced arrhythmias in rats. Objective: Our aims were to confirm that the antiarrhythmic effects of zacopride are mediated by selectively enhancing IK1 in rabbits. Methods: The effects of zacopride on the function of the main ion channels were investigated using a whole-cell patch-clamp technique in rabbits. Effects of zacopride on cardiac arrhythmias were also explored experimentally both in vivo and in vitro. Results: Zacopride moderately enhanced cardiac IK1 but had no apparent action on voltage-gated sodium current (INa), L- type calcium current (ICa-L), sodium-calcium exchange current (INa/Ca), transient outward potassium current (Ito), or delayed rectifier potassium current (IK) in rabbits. Zacopride also had a marked antiarrhythmic effect in vivo and in vitro. We proved that the resting membrane potential (RMP) was hyperpolarized in the presence of 1 μmol/L zacopride, and the action potential duration (APD) at 90% repolarization (APD90) was shortened by zacopride (0.1-10 μmol/L) in a concentration- dependent manner. Furthermore, zacopride at 1 μmol/L significantly decreased the incidence of drug-induced early afterdepolarization (EAD) in rabbit ventricular myocytes. Conclusion: Zacopride is a selective agonist of rabbit cardiac IK1 and that IK1 enhancement exerts potential antiarrhythmic effects.

scholarly journals H-89 inhibits transient outward and inward rectifier potassium currents in isolated rat ventricular myocytes

2006 ◽  
Vol 148 (8) ◽  
pp. 1091-1098 ◽  
Author(s):  
Charles Pearman ◽  
William Kent ◽  
Nicolas Bracken ◽  
Munir Hussain
Keyword(s):  
Ventricular Myocytes ◽  
Potassium Currents ◽  
Inward Rectifier ◽  
Rat Ventricular Myocytes ◽  
Isolated Rat

Effects of Xinjining (心悸宁) extract on inward rectifier potassium current in ventricular myocytes of guinea pig

2010 ◽  
Vol 16 (1) ◽  
pp. 61-65
Author(s):  
Ming-jun Zhu ◽  
Guo-juan Wang ◽  
Yong-xia Wang ◽  
Jie-lin Pu ◽  
Hong-jun Liu ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Potassium Current ◽  
Ventricular Myocytes ◽  
Inward Rectifier ◽  
Inward Rectifier Potassium Current

Electrophysiologic Mechanism Underlying Action Potential Prolongation by Sevoflurane in Rat Ventricular Myocytes

2007 ◽  
Vol 107 (1) ◽  
pp. 67-74 ◽  
Author(s):  
Jee Eun Chae ◽  
Duck Sun Ahn ◽  
Myung Hee Kim ◽  
Carl Lynch ◽  
Wyun Kon Park
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Inward Rectifier ◽  
Rat Ventricular Myocytes ◽  
Steady State Inactivation ◽  
K Current ◽  
Action Potential Prolongation ◽  
Sustained Outward Current

Abstract Background: Despite prolongation of the QTc interval in humans during sevoflurane anesthesia, little is known about the mechanisms that underlie these actions. In rat ventricular myocytes, the effect of sevoflurane on action potential duration and underlying electrophysiologic mechanisms were investigated. Methods: The action potential was measured by using a current clamp technique. The transient outward K+ current was recorded during depolarizing steps from −80 mV, followed by brief depolarization to −40 mV and then depolarization up to +60 mV. The voltage dependence of steady state inactivation was determined by using a standard double-pulse protocol. The sustained outward current was obtained by addition of 5 mm 4-aminopyridine. The inward rectifier K+ current was recorded from a holding potential of −40 mV before their membrane potential was changed from −130 to 0 mV. Sevoflurane actions on L-type Ca2+ current were also obtained. Results: Sevoflurane prolonged action potential duration, whereas the amplitude and resting membrane potential remained unchanged. The peak transient outward K+ current at +60 mV was reduced by 18 ± 2% (P &lt; 0.05) and 24 ± 2% (P &lt; 0.05) by 0.35 and 0.7 mm sevoflurane, respectively. Sevoflurane had no effect on the sustained outward current. Whereas 0.7 mm sevoflurane did not shift the steady state inactivation curve, it accelerated the current inactivation (P &lt; 0.05). The inward rectifier K+ current at −130 mV was little altered by 0.7 mm sevoflurane. L-type Ca2+ current was reduced by 28 ± 3% (P &lt; 0.05) and 33 ± 1% (P &lt; 0.05) by 0.35 and 0.7 mm sevoflurane, respectively. Conclusions: Action potential prolongation by clinically relevant concentrations of sevoflurane is due to the suppression of transient outward K+ current in rat ventricular myocytes.

Effect of Intravenous Anesthetics on Inward Rectifier Potassium Current in Rat and Human Ventricular Myocytes 

1997 ◽  
Vol 87 (2) ◽  
pp. 327-334 ◽  
Author(s):  
Cynthia A. Carnes ◽  
William Muir ◽  
David R. Van Wagoner
Keyword(s):  
Potassium Current ◽  
Ventricular Myocytes ◽  
Plasma Concentrations ◽  
Dependent Manner ◽  
Patch Clamp Technique ◽  
Concentration Dependent Manner ◽  
Pipette Solution ◽  
Rat Ventricular Myocytes ◽  
Ventricular Cells ◽  
Drug Concentrations

Background Inhibition of the inward rectifying potassium current (I(K1)) may cause cardiac dysrhythmias by decreasing resting membrane potential or prolonging action potential. Methods The effects of thiopental, ketamine, and propofol on I(K1) conductance were evaluated in rat ventricular myocytes. The effect of thiopental on I(K1) conductance was also evaluated in human ventricular myocytes. Currents were recorded using the nystatin-perforated whole-cell patch-clamp technique (holding potential, -50 mV; test potentials, -140 to -40 mV). Pipette solution contained 130 mM KCl, 5 mM MgCl2, 5 mM HEPES, and 5 mM EGTA,pH 7.2. Bath solution (32 degrees C) contained 134 mM NaCI, 4 mM KCl, 1 mM MgCl2, 1 mM CaCl2, 0.3 mM CdCl2, 5 mM HEPES, and 5 mM d-glucose,pH 7.4. Drug concentrations examined encompassed the range of clinically relevant unbound plasma concentrations. Currents were normalized for cell capacitance. Conductance was calculated as current density/delta mV from -140 to -100 mV. Analysis of variance was used to test for changes in conductance as a function of drug concentration. Results Thiopental reduced I(K1) conductance in a concentration-dependent manner (P &lt; 0.0001). Thiopental-induced changes in I(K1) conductance in rat ventricular myocytes were fit to an inhibitory E(max) model, with a median inhibitory concentration of 10.5 microM. The effect of thiopental on I(K1) conductance in human ventricular cells was comparable to that observed in rat ventricular myocytes. Neither ketamine nor propofol altered I(K1) conductance. Conclusions Thiopental reduces I(K1) conductance in a concentration-dependent manner at clinically relevant concentrations in both rat and human ventricular myocytes.

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