scholarly journals Role of action potential configuration and the contribution of Ca2+and K+currents to isoprenaline-induced changes in canine ventricular cells

2012 ◽  
Vol 167 (3) ◽  
pp. 599-611 ◽  
Author(s):  
N Szentandrássy ◽  
V Farkas ◽  
L Bárándi ◽  
B Hegyi ◽  
F Ruzsnavszky ◽  
...  
Keyword(s):  
Action Potential ◽  
Ventricular Cells ◽  
Induced Changes ◽  
K Currents ◽  
Action Potential Configuration

Adenosine-induced changes in atrial action potential: contribution of Ca and K currents

1990 ◽  
Vol 258 (4) ◽  
pp. H1070-H1078 ◽  
Author(s):  
S. Visentin ◽  
S. N. Wu ◽  
L. Belardinelli
Keyword(s):  
Action Potential ◽  
Potassium Current ◽  
Potential Contribution ◽  
Strongly Correlated ◽  
Patch Clamp Technique ◽  
Relative Contribution ◽  
Whole Cell Patch Clamp ◽  
Maximum Decrease ◽  
Induced Changes ◽  
K Currents

In this study, we examined the relative contribution of the increase in acetylcholine-regulated potassium current (IK ACh) and decrease in calcium current (ICa) to the adenosine (Ado)-induced shortening of action potential duration (APD). In isolated guinea pig atrial myocytes, membrane potentials and currents were measured by the whole cell patch-clamp technique. ICa and IK ACh were individualized by blocking the K currents with Cs+ and ICa with Cd2+. The effects of Ado on membrane potential and currents were concentration dependent. Ado (10 microM) shortened APD at 0 mV and at 90% of repolarization (APD0,90) to 7 +/- 1 and 26 +/- 6 ms from control values of 23 +/- 3 and 89 +/- 6 ms, respectively. Concomitant with the changes in APD, Ado decreased ICa from -9.2 +/- 1.3 to -6.8 +/- 10 microA/microF (26% decrease) but increased IK ACh from +3.5 +/- 0.5 to +7.8 +/- 0.8 microA/microF (123% increase). When rundown of ICa was taken into account, the maximum decrease in ICa caused by Ado was 12%. The effect of Ado on ICa and IK ACh was not altered by treatment of the cells with either Cs+ or Cd2+. The shortening of ADP0,90 strongly correlated with the increase in IK ACh but minimally with the decrease in ICa. A 22% reduction in ICa caused by lowering extracellular Ca2+ concentration ([Ca2+]o) from 3.6 to 1.8 mM was associated with an 11 and 14% shortening of APD0 and APD90, respectively. In the same myocytes an 18% decrease in ICa by 10 microM Ado reduced APD0 and APD90 by 58 and 61%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract 247: Dose-dependent Role of Inwardly Rectifying Potassium Current on Cardiac Automaticity of Human Embryonic Stem Cell-derived Cardiomyocytes

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Jidong Fu ◽  
Adrienne Dennis
Keyword(s):  
Action Potential ◽  
Potassium Current ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Ventricular Cells ◽  
Fire Action Potential ◽  
Cardiac Automaticity ◽  
Inwardly Rectifying ◽  
Dose Dependent

The inwardly rectifying potassium current (IK1), encode by Kir2 family, is responsible for maintaining the negative resting potential, and contributes to phase 3 repolarization of the cardiac action potential. IK1 was generally thought to suppress cardiac automaticity, while the suppression of IK1 in adult ventricular cardiomyocytes (CMs) could engineer bio-artificial pacemaker-like cells to spontaneously fire action potential. Our studies also showed that overexpressed the gene of Kir2.1 could facilitate the electrophysiological maturing of mouse and human embryonic stem cell-differentiated CMs (ESC-CMs), which have the high degree of automaticity with nearly 50% of cells that can spontaneously fire action potential. In this study, we extensively analyzed the electrophysiology of mouse and human ESC-CMs, and found that the maximum diastolic potential in spontaneously firing ESC-CMs, -72.1±1.3 mV in atrial cells and -75.0±2.1 mV in ventricular cells, were significantly more hyperpolarized than that in quiescent ESC-CMs (-64.4±2.1 mV in atrial cells and -67.1±3.2 mV in ventricular cells). Applying a small amount of IK1 to hyperpolarize the membrane potential could enable those quiescent ESC-CMs to spontaneously fire action potential, indicating the enhancement of cardiac automaticity, while a large amount of IK1 could quiet those spontaneously firing cells down. By combining computational and experimental analyses, we confirmed that the synergistic interaction of IK1 and pacemaker current (If) could efficiently regulate cardiac automaticity during the differentiation. Our studies disclosed a dose-dependent role of IK1 on cardiac automaticity that a small amount of IK1 enhances and a large amount of IK1 suppresses cardiac automaticity in ESC-CMs during differentiation.

Abstract 207: Mitochondrial Calcium Flux is Arrhythmogenic in Nonischemic Cardiomyopathy

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
an xie ◽  
Qiongyin Wang ◽  
Hong Liu ◽  
Lianzhi Gu ◽  
Man Liu ◽  
...  
Keyword(s):  
Salt Water ◽  
Fluorescent Imaging ◽  
Calcium Flux ◽  
Mitochondrial Calcium ◽  
Nonischemic Cardiomyopathy ◽  
Premature Ventricular Contractions ◽  
Ventricular Cells ◽  
Trigger Activity ◽  
K Currents

Introduction: Mitochondria participate in Ca2+ homeostasis and Ca2+ oscillations are thought to be involved in arrhythmogenesis. Nevertheless, the role of mitochondria in arrhythmogenesis is unclear. We have reported spontaneous and induced arrhythmias in a mouse model of nonischemic cardiomyopathy, so we investigated the role of mitochondrial Ca2+ handling in arrhythmias in this model. Methods: Nonischemic cardiomyopathy was induced in C57BL/6 mice by 6 weeks of hypertension evoked after unilateral nephrectomy, deoxycorticosterone acetate (DOCA) pellet implantation, and 1% salt water substitution. Sham operated mice were used as controls. ECG telemetry recording was used to monitor arrhythmias from DOCA mice and 7 sham mice at 18 weeks of age. Action potentials (APs) were recorded by perforated current-clamp in isolated mouse ventricular cells. Potassium and L-type Ca2+ currents were measured by voltage-clamp. Changes in cytoplasmic and mitochondrial Ca2+ were determined by fluorescent imaging using Fluo-4 and Rhod-2, respectively, in isolated ventricular cells. Results: Seven DOCA mice and two sham mice had isoproterenol (0.5 mg/kg)-induced premature ventricular contractions (PVCs, p<0.05). Three DOCA mice and no sham mice had isoproterenol (2.5 mg/kg)-induced ventricular fibrillation. QTc was significantly prolonged from 41.9 ±1.4 in sham mice to 52.0 ± 2.1 ms in DOCA mice. At the cellular levels, myocytes had a prominent increase of APD90 from 66.6 ± 21.1 to 311.8 ± 44.9 ms, explained by augmented L-type Ca2+ current and decreased total K+ currents. Two of 12 sham mice ventricular cells and 8 from 12 DOCA mice ventricular cells had EADs (p<0.05). Three of 12 DOCA mice but none of the sham myocytes had PVCs with stimulated APs. Trigger activity could be abolished by 10 µM Ru360, a mitochondrial calcium uniporter specific antagonist. Ru360 had no effect on L-type Ca2+ current, total K+ currents, or APD90. Ru360 inhibited mitochondrial Ca2+ uptake in DOCA mice ventricular cells, implicating mitochondrial Ca2+ release in modulating the arrhythmic risk. Conclusions: Mitochondrial Ca2+ handling appears to play an important role in triggered activity and may be important in the incidence of ventricular arrhythmias in nonischemic cardiomyopathy.

TransmembraneI Ca contributes to rate-dependent changes of action potentials in human ventricular myocytes

1999 ◽  
Vol 276 (1) ◽  
pp. H98-H106 ◽  
Author(s):  
Gui-Rong Li ◽  
Baofeng Yang ◽  
Jianlin Feng ◽  
Ralph F. Bosch ◽  
Michel Carrier ◽  
...  
Keyword(s):  
Action Potential ◽  
Ventricular Myocytes ◽  
Slow Component ◽  
Cell Voltage ◽  
High Rate ◽  
Delayed Rectifier ◽  
Rate Dependent ◽  
Ventricular Cells ◽  
The Right

The mechanism of action potential abbreviation caused by increasing rate in human ventricular myocytes is unknown. The present study was designed to determine the potential role of Ca2+ current ( I Ca) in the rate-dependent changes in action potential duration (APD) in human ventricular cells. Myocytes isolated from the right ventricle of explanted human hearts were studied at 36°C with whole cell voltage and current-clamp techniques. APD at 90% repolarization decreased by 36 ± 4% when frequency increased from 0.5 to 2 Hz. Equimolar substitution of Mg2+ for Ca2+ significantly decreased rate-dependent changes in APD (to 6 ± 3%, P < 0.01). Peak I Ca was decreased by 34 ± 3% from 0.5 to 2 Hz ( P < 0.01), and I Ca had recovery time constants of 65 ± 12 and 683 ± 39 ms at −80 mV. Action potential clamp demonstrated a decreasing contribution of I Ca during the action potential as rate increased. The rate-dependent slow component of the delayed rectifier K+current ( I Ks) was not observed in four cells with an increase in frequency from 0.5 to 3.3 Hz, perhaps because the I Ks is so small that the increase at a high rate could not be seen. These results suggest that reduction of Ca2+influx during the action potential accounts for most of the rate-dependent abbreviation of human ventricular APD.

Two types of action potential configuration in single cardiac Purkinje cells of sheep

1999 ◽  
Vol 277 (4) ◽  
pp. H1299-H1310 ◽  
Author(s):  
Arie O. Verkerk ◽  
Marieke W. Veldkamp ◽  
Fabio Abbate ◽  
Gudrun Antoons ◽  
Lennart N. Bouman ◽  
...  
Keyword(s):  
Action Potential ◽  
Purkinje Cells ◽  
Action Potentials ◽  
Phase 1 ◽  
Stimulus Frequency ◽  
Ventricular Cells ◽  
Cardiac Purkinje Cells ◽  
Current Densities ◽  
Lp Cells ◽  
Action Potential Configuration

Membrane potentials and currents of isolated sheep Purkinje and ventricular cells were compared using patch-clamp and microelectrode techniques. In ∼50% of Purkinje cells, we observed action potentials that showed a prominent phase 1 repolarization and relatively negative plateau (LP cells). Action potential configuration of the remaining Purkinje cells was characterized by little phase 1 repolarization and relatively positive plateau (HP cells). Microelectrode impalement of Purkinje strands also revealed these two types of action potential configuration. In LP cells, the density of L-type Ca2+ current ( I Ca,L) was lower, whereas the density of transient outward K+ current was higher, than in HP cells. Action potentials of HP cells strongly resembled those of ventricular cells. Densities of inward rectifier current and I Ca,L were significantly higher in ventricular cells compared with densities in both LP and HP Purkinje cells. Differences in current densities explain the striking differences in action potential configuration and the stimulus frequency dependency thereof that we observed in LP, HP, and ventricular cells. We conclude that LP Purkinje cells, HP Purkinje cells, and ventricular cells of sheep each have a unique action potential configuration.

An ionic model of stretch-activated and stretch-modulated currents in rabbit ventricular myocytes

EP Europace ◽  
2005 ◽  
Vol 7 (s2) ◽  
pp. S128-S134 ◽  
Author(s):  
Sarah N. Healy ◽  
Andrew D. McCulloch
Keyword(s):  
Action Potential ◽  
Safety Factor ◽  
Ventricular Myocytes ◽  
Reversal Potential ◽  
Ionic Model ◽  
Rabbit Ventricular Myocytes ◽  
Induced Changes ◽  
Transmural Heterogeneity ◽  
Action Potential Shortening

Abstract Aims To develop an ionic model of stretch-activated and stretch-modulated currents in rabbit ventricular myocytes consistent with experimental observations, that can be used to investigate the role of these currents in intact myocardium. Methods and results A non-specific cation-selective stretch-activated current Ins, was incorporated into the Puglisi–Bers ionic model of epicardial, endocardial and midmyocardial ventricular myocytes. Using the model, we predict a reduction in action potential duration at 20% repolarization (APD20) and action potential amplitude, an elevated resting transmembrane potential and either an increase or decrease in APD90, depending on the reversal potential of Ins. A stretch-induced decrease in IK1 (70%), plus a small Ins current (gns=10 pS), results in a reduction in APD20 and increase in APD90, and a reduced safety factor for conduction. Increasing IK1 (150%) plus a large Ins current (gns=40 pS), also leads to a reduction in APD20 and increase in APD90, but with a greater safety factor. Endocardial and midmyocardial cells appear to be the most sensitive to stretch-induced changes in action potential. The addition of the K+-specific stretch-activated current (SAC) IKo results in action potential shortening. Conclusion Transmural heterogeneity of IKo may reduce repolarization gradients in intact myocardium caused by intrinsic ion channel densities, nonuniform strains and electrotonic effects.

Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells

2012 ◽  
Vol 386 (3) ◽  
pp. 239-246 ◽  
Author(s):  
László Szabó ◽  
Norbert Szentandrássy ◽  
Kornél Kistamás ◽  
Bence Hegyi ◽  
Ferenc Ruzsnavszky ◽  
...  
Keyword(s):  
Action Potential ◽  
Ion Currents ◽  
Ventricular Cells ◽  
Action Potential Configuration

Effect of simulated Ito on guinea pig and canine ventricular action potential morphology

2006 ◽  
Vol 291 (2) ◽  
pp. H631-H637 ◽  
Author(s):  
Min Dong ◽  
Xiaoyin Sun ◽  
Astrid A. Prinz ◽  
Hong-Sheng Wang
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Ventricular Myocytes ◽  
Phase 1 ◽  
Outward Current ◽  
Transient Outward Current ◽  
Ventricular Cells ◽  
Perforated Patch Clamp ◽  
Ventricular Action Potential

The transient outward current ( Ito) is a major repolarizing current in the heart. Marked reduction of Ito density occurs in heart failure and is accompanied by significant action potential duration (APD) prolongation. To understand the species-dependent role of Ito in regulating the ventricular action potential morphology and duration, we introduced simulated Ito conductance in guinea pig and canine endocardial ventricular myocytes using the dynamic clamp technique and perforated patch-clamp recordings. The effects of simulated Ito in both types of cells were complex and biphasic, separated by a clear density threshold of ∼40 pA/pF. Below this threshold, simulated Ito resulted in a distinct phase 1 notch and had little effect on or moderately prolonged the APD. Ito above the threshold resulted in all-or-none repolarization and precipitously reduced the APD. Qualitatively, these results agreed with our previous studies in canine ventricular cells using whole cell recordings. We conclude that 1) contrary to previous gene transfer studies involving the Kv4.3 current, the response of guinea pig ventricular myocytes to a fully inactivating Ito is similar to that of canine ventricular cells and 2) in animals such as dogs that have a broad cardiac action potential, Ito does not play a major role in setting the APD.

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