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.

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 Selective inhibition of physiological late Na+ current stabilizes ventricular repolarization

2018 ◽  
Vol 314 (2) ◽  
pp. H236-H245 ◽  
Author(s):  
Nesrine El-Bizri ◽  
Cindy Hong Li ◽  
Gong-Xin Liu ◽  
Sridharan Rajamani ◽  
Luiz Belardinelli
Keyword(s):  
Action Potential ◽  
Cardiac Myocytes ◽  
Ventricular Myocytes ◽  
Physiological Role ◽  
Selective Inhibition ◽  
Ventricular Repolarization ◽  
Delayed Rectifier ◽  
Pharmacological Agents ◽  
Isolated Hearts ◽  
Qt Intervals

The physiological role of cardiac late Na+ current ( INa) has not been well described. In this study, we tested the hypothesis that selective inhibition of physiological late INa abbreviates the normal action potential (AP) duration (APD) and counteracts the prolongation of APD and arrhythmic activities caused by inhibition of the delayed rectifier K+ current ( IKr). The effects of GS-458967 (GS967) on the physiological late INa and APs in rabbit isolated ventricular myocytes and on the monophasic APs and arrhythmias in rabbit isolated perfused hearts were determined. In ventricular myocytes, GS967 and, for comparison, tetrodotoxin concentration dependently decreased the physiological late INa with IC50 values of 0.5 and 1.9 µM, respectively, and significantly shortened the APD measured at 90% repolarization (APD90). A strong correlation between inhibition of the physiological late INa and shortening of APD by GS967 or tetrodotoxin ( R2 of 0.96 and 0.97, respectively) was observed. Pretreatment of isolated myocytes or hearts with GS967 (1 µM) significantly shortened APD90 and monophasic APD90 and prevented the prolongation and associated arrhythmias caused by the IKr inhibitor E4031 (1 µM). In conclusion, selective inhibition of physiological late INa shortens the APD, stabilizes ventricular repolarization, and decreases the proarrhythmic potential of pharmacological agents that slow ventricular repolarization. Thus, selective inhibition of late INa may constitute a generalizable approach to stabilize ventricular repolarization and suppress arrhythmogenicity associated with conditions whereby AP or QT intervals are prolonged. NEW & NOTEWORTHY The contribution of physiological late Na+ current in action potential duration (APD) of rabbit cardiac myocytes was estimated. The inhibition of this current prevented the prolongation of APD in rabbit cardiac myocytes, the prolongation of monophasic APD, and generation of arrhythmias in rabbit isolated hearts caused by delayed rectifier K+ current inhibition.

Altered K+ current profiles underlie cardiac action potential shortening in hyperkalemia and β-adrenergic stimulation

2019 ◽  
Vol 97 (8) ◽  
pp. 773-780 ◽  
Author(s):  
Bence Hegyi ◽  
Ye Chen-Izu ◽  
Leighton T. Izu ◽  
Tamás Bányász
Keyword(s):  
Action Potential ◽  
Ventricular Myocytes ◽  
Delayed Rectifier ◽  
Adrenergic Stimulation ◽  
Compensatory Mechanisms ◽  
Phase 3 ◽  
K Current ◽  
Rabbit Ventricular Myocytes ◽  
Action Potential Shortening ◽  
Stimulation Of

Hyperkalemia is known to develop in various conditions including vigorous physical exercise. In the heart, hyperkalemia is associated with action potential (AP) shortening that was attributed to altered gating of K+ channels. However, it remains unknown how hyperkalemia changes the profiles of each K+ current under a cardiac AP. Therefore, we recorded the major K+ currents (inward rectifier K+ current, IK1; rapid and slow delayed rectifier K+ currents, IKr and IKs, respectively) using AP-clamp in rabbit ventricular myocytes. As K+ may accumulate at rapid heart rates during sympathetic stimulation, we also examined the effect of isoproterenol on these K+ currents. We found that IK1 was significantly increased in hyperkalemia, whereas the reduction of driving force for K+ efflux dominated over the altered channel gating in case of IKr and IKs. Overall, the markedly increased IK1 in hyperkalemia overcame the relative decreases of IKr and IKs during AP, resulting in an increased net repolarizing current during AP phase 3. β-Adrenergic stimulation of IKs also provided further repolarizing power during sympathetic activation, although hyperkalemia limited IKs upregulation. These results indicate that facilitation of IK1 in hyperkalemia and β-adrenergic stimulation of IKs represent important compensatory mechanisms against AP prolongation and arrhythmia susceptibility.

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.

Characterization and functional consequences of delayed rectifier current transient in ventricular repolarization

2000 ◽  
Vol 278 (3) ◽  
pp. H806-H817 ◽  
Author(s):  
Gary A. Gintant
Keyword(s):  
Action Potential ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Inward Rectifier ◽  
Ventricular Repolarization ◽  
Delayed Rectifier ◽  
Voltage Range ◽  
Delayed Rectifier Current ◽  
Recovery From Inactivation ◽  
Voltage Dependent

Although inactivation of the rapidly activating delayed rectifier current ( I Kr) limits outward current on depolarization, the role of I Kr (and recovery from inactivation) during repolarization is uncertain. To characterize I Krduring ventricular repolarization (and compare with the inward rectifier current, I K1), voltage-clamp waveforms simulating the action potential were applied to canine ventricular, atrial, and Purkinje myocytes. In ventricular myocytes, I Kr was minimal at plateau potentials but transiently increased during repolarizing ramps. The I Kr transient was unaffected by repolarization rate and maximal after 150-ms depolarizations (+25 mV). Action potential clamps revealed the I Kr transient terminating the plateau. Although peak I Kr transient density was relatively uniform among myocytes, potentials characterizing the peak transients were widely dispersed. In contrast, peak inward rectifier current ( I K1) density during repolarization was dispersed, whereas potentials characterizing I K1 defined a narrower (more negative) voltage range. In summary, rapidly activating I Kr provides a delayed voltage-dependent (and functionally time-independent) outward transient during ventricular repolarization, consistent with rapid recovery from inactivation. The heterogeneous voltage dependence of I Kr provides a novel means for modulating the contribution of this current during repolarization.

Temperature-dependent expression of sarcolemmal K+ currents in rainbow trout atrial and ventricular myocytes

2002 ◽  
Vol 282 (4) ◽  
pp. R1191-R1199 ◽  
Author(s):  
Matti Vornanen ◽  
Ari Ryökkynen ◽  
Antti Nurmi
Keyword(s):  
Rainbow Trout ◽  
Cardiac Myocytes ◽  
Molecular Mechanisms ◽  
Ventricular Myocytes ◽  
Cardiac Contractility ◽  
Temperature Acclimation ◽  
Delayed Rectifier ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Delayed Rectifier Current ◽  
Ventricular Cells

Temperature has a strong influence on the excitability and the contractility of the ectothermic heart that can be alleviated in some species by temperature acclimation. The molecular mechanisms involved in the temperature-induced improvement of cardiac contractility and excitability are, however, still poorly known. The present study examines the role of sarcolemmal K+ currents from rainbow trout ( Oncorhynchus mykiss) cardiac myocytes after thermal acclimation. The two major K+ conductances of the rainbow trout cardiac myocytes were identified as the Ba2+-sensitive background inward rectifier current ( I K1) and the E-4031-sensitive delayed rectifier current ( I Kr). In atrial cells, the density of I K1 is very low and the density of I Kr is remarkably high. The opposite is true for ventricular cells. Acclimation to cold (4°C) modified the two K+ currents in opposite ways. Acclimation to cold increases the density of I Kr and depresses the density of I K1. These changes in repolarizing K+ currents alter the shape of the action potential, which is much shorter in cold-acclimated than warm-acclimated (17°C) trout. These results provide the first concrete evidence that K+channels of trout cardiac myocytes are adaptable units that provide means to regulate cardiac excitability and contractility as a function of temperature.

Electrophysiological and functional effects of adenosine on ventricular myocytes of various mammalian species

1996 ◽  
Vol 271 (4) ◽  
pp. C1233-C1243 ◽  
Author(s):  
Y. Song ◽  
L. Belardinelli
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Ventricular Myocytes ◽  
Mammalian Species ◽  
Outward Current ◽  
Binding Studies ◽  
Outward Currents ◽  
K Current ◽  
Rabbit Ventricular Myocytes ◽  
A1 Adenosine Receptors

The goal of this study was to determine the electrophysiological and functional effects of adenosine on ventricular myocytes of guinea pig, rabbit, rat, and ferret hearts. Adenosine (100 microM) shortened the action potential durations of rat and ferret myocytes by 14 +/- 1 and 57 +/- 7%, reduced the amplitudes of cell twitch shortening by 13 +/- 1 and 54 +/- 5%, and increased outward currents by 15 +/- 4 and 55 +/- 5%, respectively, but had no effect on guinea pig and rabbit myocytes. The properties of adenosine-activated outward current in rat and ferret ventricular myocytes indicated that this current is the adenosine-sensitive K+ current [IK(Ado)]. Adenosine had no significant effect on basal Ca2+ current but specifically inhibited isoproterenol-stimulated L-type Ca2+ current in myocytes of all species studied. Binding studies revealed that the density of A1 adenosine receptors (A1AdoR) was highest in ferret and lowest in rabbit myocytes, but the differential effects of adenosine among species could not be solely explained by differences in A1AdoR density. In summary, adenosine shortened the action potential and reduced the twitch shortening of rat and ferret but not of guinea pig and rabbit ventricular myocytes. Shortening of the action potential was associated with the activation of IK(Ado). The anti-beta-adrenergic action of adenosine appeared to be independent of species.

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