scholarly journals Canine Myocytes Represent a Good Model for Human Ventricular Cells Regarding Their Electrophysiological Properties

2021 ◽  
Vol 14 (8) ◽  
pp. 748
Author(s):  
Péter P. Nánási ◽  
Balázs Horváth ◽  
Fábián Tar ◽  
János Almássy ◽  
Norbert Szentandrássy ◽  
...  
Keyword(s):  
Action Potential ◽  
Time Course ◽  
Laboratory Animals ◽  
Delayed Rectifier ◽  
Ion Currents ◽  
Human Cardiomyocytes ◽  
Ventricular Cells ◽  
Repolarization Reserve ◽  
Electrophysiological Studies ◽  
K Current

Due to the limited availability of healthy human ventricular tissues, the most suitable animal model has to be applied for electrophysiological and pharmacological studies. This can be best identified by studying the properties of ion currents shaping the action potential in the frequently used laboratory animals, such as dogs, rabbits, guinea pigs, or rats, and comparing them to those of human cardiomyocytes. The authors of this article with the experience of three decades of electrophysiological studies, performed in mammalian and human ventricular tissues and isolated cardiomyocytes, summarize their results obtained regarding the major canine and human cardiac ion currents. Accordingly, L-type Ca2+ current (ICa), late Na+ current (INa-late), rapid and slow components of the delayed rectifier K+ current (IKr and IKs, respectively), inward rectifier K+ current (IK1), transient outward K+ current (Ito1), and Na+/Ca2+ exchange current (INCX) were characterized and compared. Importantly, many of these measurements were performed using the action potential voltage clamp technique allowing for visualization of the actual current profiles flowing during the ventricular action potential. Densities and shapes of these ion currents, as well as the action potential configuration, were similar in human and canine ventricular cells, except for the density of IK1 and the recovery kinetics of Ito. IK1 displayed a largely four-fold larger density in canine than human myocytes, and Ito recovery from inactivation displayed a somewhat different time course in the two species. On the basis of these results, it is concluded that canine ventricular cells represent a reasonably good model for human myocytes for electrophysiological studies, however, it must be borne in mind that due to their stronger IK1, the repolarization reserve is more pronounced in canine cells, and moderate differences in the frequency-dependent repolarization patterns can also be anticipated.

Dual effects of external magnesium on action potential duration in guinea pig ventricular myocytes

1995 ◽  
Vol 268 (6) ◽  
pp. H2321-H2328 ◽  
Author(s):  
S. Zhang ◽  
T. Sawanobori ◽  
H. Adaniya ◽  
Y. Hirano ◽  
M. Hiraoka
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Decay Time ◽  
Action Potential Duration ◽  
Time Course ◽  
Ventricular Myocytes ◽  
Membrane Surface ◽  
Surface Charges ◽  
Whole Cell Patch Clamp ◽  
K Current

Effects of extracellular magnesium (Mg2+) on action potential duration (APD) and underlying membrane currents in guinea pig ventricular myocytes were studied by using the whole cell patch-clamp method. Increasing external Mg2+ concentration [Mg2+]o) from 0.5 to 3 mM produced a prolongation of APD at 90% repolarization (APD90), whereas 5 and 10 mM Mg2+ shortened it. [Mg2+]o, at 3 mM or higher, suppressed the delayed outward K+ current and the inward rectifier K+ current. Increases in [Mg2+]o depressed the peak amplitude and delayed the decay time course of the Ca2+ current (ICa), the latter effect is probably due to the decrease in Ca(2+)-induced inactivation. Thus 3 mM Mg2+ suppressed the peak ICa but increased the late ICa amplitude at the end of a 200-ms depolarization pulse, whereas 10 mM Mg2+ suppressed both components. Application of 10 mM Mg2+ shifted the voltage-dependent activation and inactivation by approximately 10 mV to more positive voltage due to screening the membrane surface charges. Application of manganese (1-5 mM) also caused dual effects on APD90, similar to those of Mg2+, and suppressed the peak ICa with slowed decay. These results suggest that the dual effects of Mg2+ on APD in guinea pig ventricular myocytes can be, at least in part, explained by its action on ICa with slowed decay time course in addition to suppressive effects on K+ currents.

Outward currents in normal and hypertrophied feline ventricular myocytes

1989 ◽  
Vol 256 (5) ◽  
pp. H1450-H1461 ◽  
Author(s):  
R. B. Kleiman ◽  
S. R. Houser
Keyword(s):  
Time Course ◽  
Ventricular Myocytes ◽  
Pressure Overload ◽  
Negative Slope ◽  
Inward Rectification ◽  
Delayed Rectifier ◽  
Outward Currents ◽  
K Current ◽  
Prolongation Of Action Potential ◽  
The Right

The properties of the inward rectifier K current (IK1) and the delayed rectifier K current (IK) were studied in single feline myocytes isolated from the right ventricle of normal cats and cats with experimentally induced right ventricular hypertrophy (RVH). IK1 demonstrated time-dependent decay during hyperpolarizations and showed inward rectification with a prominent negative-slope region between -30 and -10 mV. Both IK1 and IK was carried primarily by K ions. The activation of IK during depolarizations followed a monoexponential time course, whereas the deactivation of IK tail currents was either mono- or biexponential depending on the repolarization potential. IK showed marked rectification at positive potentials. A comparison of these currents in normal and hypertrophy myocytes revealed that in RVH the magnitude of IK1 is increased, whereas the magnitude of IK is decreased. IK showed steeper rectification, had slower activation, and had more rapid deactivation in RVH. These abnormalities of the IK may contribute to the prolongation of action potential duration, which characterizes pressure-overload cardiac hypertrophy.

scholarly journals A time- and voltage-dependent K+ current in single cardiac cells from bullfrog atrium.

1986 ◽  
Vol 88 (6) ◽  
pp. 777-798 ◽  
Author(s):  
J R Hume ◽  
W Giles ◽  
K Robinson ◽  
E F Shibata ◽  
R D Nathan ◽  
...  
Keyword(s):  
Time Course ◽  
Voltage Dependence ◽  
Outward Current ◽  
Cardiac Cells ◽  
Delayed Rectifier ◽  
Mechanical Dispersion ◽  
Atrial Cells ◽  
Voltage Dependent ◽  
K Current ◽  
Kinetics Of

Individual myocytes were isolated from bullfrog atrium by enzymatic and mechanical dispersion, and a one-microelectrode voltage clamp was used to record the slow outward K+ currents. In normal [K+]o (2.5 mM), the slow outward current tails reverse between -95 and -100 mV. This finding, and the observed 51-mV shift of Erev/10-fold change in [K+]o, strongly suggest that the "delayed rectifier" in bullfrog atrial cells is a K+ current. This current, IK, plays an important role in initiating repolarization, and it is distinct from the quasi-instantaneous, inwardly rectifying background current, IK. In atrial cells, IK does not exhibit inactivation, and very long depolarizing clamp steps (20 s) can be applied without producing extracellular K+ accumulation. The possibility of [K+]o accumulation contributing to these slow outward current changes was assessed by (a) comparing reversal potentials measured after short (2 s) and very long (15 s) activating prepulses, and (b) studying the kinetics of IK at various holding potentials and after systematically altering [K+]o. In the absence of [K+]o accumulation, the steady state activation curve (n infinity) and fully activated current-voltage (I-V) relation can be obtained directly. The threshold of the n infinity curve is near -50 mV, and it approaches a maximum at +20 mV; the half-activation point is approximately -16 mV. The fully activated I-V curve of IK is approximately linear in the range -40 to +30 mV. Semilog plots of the current tails show that each tail is a single-exponential function, which suggests that only one Hodgkin-Huxley conductance underlies this slow outward current. Quantitative analysis of the time course of onset of IK and of the corresponding envelope of tails demonstrate that the activation variable, n, must be raised to the second power to fit the sigmoid onset accurately. The voltage dependence of the kinetics of IK was studied by recording and curve-fitting activating and deactivating (tail) currents. The resulting 1/tau n curve is U-shaped and somewhat asymmetric; IK exhibits strong voltage dependence in the diastolic range of potentials. Changes in the [Ca2+]o in the superfusing Ringer's, and/or addition of La3+ to block the transmembrane Ca2+ current, show that the time course and magnitude of IK are not significantly modulated by transmembrane Ca2+ movements, i.e., by ICa. These experimentally measured voltage- and time-dependent descriptors of IK strongly suggest an important functional role for IK in atrial tissue: it initiates repolarization and can be an important determinant of rate-induced changes in action potential duration.

scholarly journals Lipopolysaccharide prolongs action potential duration in HL-1 mouse cardiomyocytes

2012 ◽  
Vol 303 (8) ◽  
pp. C825-C833 ◽  
Author(s):  
Robert Wondergem ◽  
Bridget M. Graves ◽  
Chuanfu Li ◽  
David L. Williams
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Salmonella Enteritidis ◽  
Time Course ◽  
Outward Current ◽  
Cell Voltage ◽  
Delayed Rectifier ◽  
Maximal Effect ◽  
Cellular Mechanisms ◽  
Whole Cell

Sepsis has deleterious effects on cardiac function including reduced contractility. We have shown previously that lipopolysaccharides (LPS) directly affect HL-1 cardiac myocytes by inhibiting Ca2+ regulation and by impairing pacemaker “funny” current, If. We now explore further cellular mechanisms whereby LPS inhibits excitability in HL-1 cells. LPS (1 μg/ml) derived from Salmonella enteritidis decreased rate of firing of spontaneous action potentials in HL-1 cells, and it increased their pacemaker potential durations and decreased their rates of depolarization, all measured by whole cell current clamp. LPS also increased action potential durations and decreased their amplitude in cells paced at 1 Hz with 0.1 nA, and 20 min were necessary for maximal effect. LPS decreased the amplitude of a rapidly inactivating inward current attributed to Na+ and of an outward current attributed to K+; both were measured by whole cell voltage clamp. The K+ currents displayed a resurgent outward tail current, which is characteristic of the rapid delayed-rectifier K+ current, IKr. LPS accordingly reduced outward currents measured with pipette Cs+ substituted for K+ to isolate IKr. E-4031 (1 μM) markedly inhibited IKr in HL-1 cells and also increased action potential duration; however, the direct effects of E-4031 occurred minutes faster than the slow effects of LPS. We conclude that LPS increases action potential duration in HL-1 mouse cardiomyocytes by inhibition of IKr and decreases their rate of firing by inhibition of INa. This protracted time course points toward an intermediary metabolic event, which either decreases available mouse ether-a-go-go (mERG) and Na+ channels or potentiates their inactivation.

The slow activating, delayed rectifier K+ current is a major component of repolarization reserve

Heart Rhythm ◽  
2005 ◽  
Vol 2 (5) ◽  
pp. S137
Author(s):  
Yejia Song ◽  
John C. Shryock ◽  
Lin Wu ◽  
Luiz Belardinelli
Keyword(s):  
Delayed Rectifier ◽  
Repolarization Reserve ◽  
K Current

Comments on “A model for human ventricular tissue”

2005 ◽  
Vol 288 (1) ◽  
pp. H453-H453
Author(s):  
Leonid Livshitz ◽  
Keith Decker ◽  
Gregory Faber ◽  
Thomas O'Hara ◽  
Jonathan Silva ◽  
...  
Keyword(s):  
Action Potential ◽  
Large Scale ◽  
Spiral Wave ◽  
Alternative Methods ◽  
Delayed Rectifier ◽  
Recent Experimental Data ◽  
M Cell ◽  
Ventricular Cells ◽  
Ventricular Tissue ◽  
Reentrant Arrhythmias

The experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. In this article we introduce a mathematical model of the action potential of human ventricular cells that, while including a high level of electrophysiological detail, is computationally cost-effective enough to be applied in large-scale spatial simulations for the study of reentrant arrhythmias. The model is based on recent experimental data on most of the major ionic currents: the fast sodium, L-type calcium, transient outward, rapid and slow delayed rectifier, and inward rectifier currents. The model includes a basic calcium dynamics, allowing for the realistic modeling of calcium transients, calcium current inactivation, and the contraction staircase. We are able to reproduce human epicardial, endocardial, and M cell action potentials and show that differences can be explained by differences in the transient outward and slow delayed rectifier currents. Our model reproduces the experimentally observed data on action potential duration restitution, which is an important characteristic for reentrant arrhythmias. The conduction velocity restitution of our model is broader than in other models and agrees better with available data. Finally, we model the dynamics of spiral wave rotation in a two-dimensional sheet of human ventricular tissue and show that the spiral wave follows a complex meandering pattern and has a period of 265 ms. We conclude that the proposed model reproduces a variety of electrophysiological behaviors and provides a basis for studies of reentrant arrhythmias in human ventricular tissue. Comments on “A model for human ventricular tissue” by K. H. W. J. ten Tusscher et al.

Identification and characteristics of delayed rectifier K+ current in fetal mouse ventricular myocytes

1996 ◽  
Vol 270 (6) ◽  
pp. H2088-H2093 ◽  
Author(s):  
L. Wang ◽  
H. J. Duff
Keyword(s):  
Action Potential ◽  
Cardiac Myocytes ◽  
Ventricular Myocytes ◽  
Dominant Role ◽  
Ventricular Myocardium ◽  
Negative Slope ◽  
Delayed Rectifier ◽  
Mouse Heart ◽  
Fetal Mouse ◽  
K Current

Although the genetics of mammalian cardiac K+ channels have been most intensively investigated in mice, there are limited data available from the electrophysiological studies of the K+ currents in native mouse cardiac myocytes, especially in fetal mouse heart. The present study utilized whole cell patch-clamp techniques to assess the delayed rectifier K+ current (IK) in fetal (18th day of gestation) mouse ventricular myocytes. IK in fetal mouse ventricular myocytes activated rapidly, displayed a negative slope conductance of the current-voltage relationships at test potentials > 0 mV, satisfied the envelope of IK-tail test for a single component, and was very sensitive to dofetilide. These characteristics confirm that this current is the rapidly activating component of IK known as IK,r. In addition, dofetilide dramatically prolonged action potential duration in single ventricular myocytes as well as in ventricular myocardium, suggesting that IK,r plays a dominant role in action potential repolarization in fetal mouse heart. From these data we can conclude that fetal mouse cardiac myocytes express IK,r, which functions as a dominant repolarizing K+ current.

Differential modulation by adenylate cyclase of Ca2+ and delayed K+ current in ventricular myocytes

1994 ◽  
Vol 266 (4) ◽  
pp. H1551-H1557 ◽  
Author(s):  
K. Harada ◽  
T. Iijima
Keyword(s):  
Adenylate Cyclase ◽  
Ventricular Myocytes ◽  
Cell Voltage ◽  
Threshold Concentration ◽  
Water Soluble ◽  
Delayed Rectifier ◽  
Differential Modulation ◽  
Beta Adrenoceptor ◽  
Ventricular Cells ◽  
K Current

This study was designed to investigate the differential modulation of the L-type Ca2+ (ICa) and the delayed rectifier K+ (IK) currents by direct activation of adenylate cyclase in guinea pig ventricular preparations. Action potentials were measured with conventional microelectrodes in excised papillary muscles. Isoproterenol significantly shortened the action potential duration at 90% repolarization (APD90) at 0.1 nM but significantly prolonged it at a higher concentration (10 nM). A water-soluble forskolin derivative, 6-(3-dimethylaminopropionyl) forskolin (NKH-477), slightly but significantly shortened APD at 12 nM but not at a higher concentration (120 nM). Effects of isoproterenol and NKH-477 on ICa and IK were also investigated by use of the whole cell voltage-clamp technique in single ventricular cells. Isoproterenol increased not only IK but also ICa at the same threshold concentration (0.3 nM). In contrast, the threshold concentration of NKH-477 for increasing IK (approximately 1 nM) was clearly lower than that for increasing ICa (10 nM). These results indicate that ICa and IK channels could be differentially regulated during beta-adrenoceptor stimulation.

Intracellular Ca2+ and protein kinase C modulate K+ current in guinea pig heart cells

1987 ◽  
Vol 253 (5) ◽  
pp. H1321-H1324 ◽  
Author(s):  
N. Tohse ◽  
M. Kameyama ◽  
H. Irisawa
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Guinea Pig ◽  
Cell Voltage ◽  
Delayed Rectifier ◽  
Heart Cells ◽  
Guinea Pig Heart ◽  
Kinase C ◽  
Ventricular Cells ◽  
K Current

Effects of protein kinase C (PKC) and intracellular calcium ion (Cai2+) on the delayed rectifier K+ current (IK) were investigated in the single ventricular cells of guinea pig by use of an internal-dialysis method and a whole cell voltage-clamp technique. 12-O-tetradecanoylphorbol-13-acetate (TPA, 10(-9) M), an activator of PKC, increased the amplitude of IK in the presence of Cai2+ higher than 10(-10) M. This effect of TPA was mimicked by a synthetic diacylglycerol, 1-oleoyl-2-acetylglycerol (OAG), 50 micrograms/ml, 125 microM, and was blocked by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (10 microM). The above findings suggest that IK channels were phosphorylated by PKC and thereby the amplitude of IK was increased. IK was also increased by elevating the concentration of Cai2+ in the absence of TPA. It is thus indicated that IK channels are modulated by Cai2+ not only through activation of PKC but also directly. Our observation may provide a possible mechanism by which Cai2+ mediates the link between the Ca2+ transients during contraction and the action potential duration.

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