Biphasic Response of Action Potential Duration to Metabolic Inhibition in Rabbit and Human Ventricular Myocytes: Role of Transient Outward Current and ATP-regulated Potassium Current

1996 ◽  
Vol 28 (12) ◽  
pp. 2443-2456 ◽  
Author(s):  
Arie O. Verkerk ◽  
Marieke W. Veldkamp ◽  
Antoni C.G. van Ginneken ◽  
Lennart N. Bouman
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Potassium Current ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Metabolic Inhibition ◽  
Transient Outward Current ◽  
Biphasic Response

Decreased transient outward K+ current in ventricular myocytes from acromegalic rats

1991 ◽  
Vol 260 (3) ◽  
pp. H935-H942 ◽  
Author(s):  
X. P. Xu ◽  
P. M. Best
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Time Course ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Resting Potential ◽  
Gh3 Cells ◽  
Heart Weight ◽  
Transient Outward Current ◽  
Tumor Bearing

Cardiac hypertrophy and heart failure are common to acromegalic patients who have abnormally high serum growth hormone (GH). While the function of cardiac muscle is clearly affected by chronically elevated GH, the electrical activity of myocytes from hearts with GH-dependent hypertrophy has not been studied. We used adult, female Wistar-Furth rats with induced GH-secreting tumors to study the effect of excessive GH on ion channels of cardiac myocytes. GH-secreting tumors were induced by subcutaneous inoculation of GH3 cells. Eight weeks after inoculation, the rats had doubled their body weight and heart size compared with age-matched controls. There were no differences in either action potential amplitude or resting potential of right ventricular myocytes from control and tumor-bearing rats. However, action potential duration increased significantly in tumor-bearing rats; the time to 50% repolarization was 23 +/- 14 ms (n = 10) compared with 6.6 +/- 1.5 ms (n = 14) in controls. The prolongation of the action potential was mainly due to a decrease in density of a transient outward current (It,o) carried by K+. The normalized conductance for It,o decreased from 0.53 +/- 0.10 nS/pF (n = 25) in controls to 0.33 +/- 0.09 nS/pF (n = 26) in tumor-bearing rats. The decrease in It,o) and increase in heart weight occurred with a similar time course. The increased action potential duration prolongs Ca2+ influx through L-type Ca2+ channels in the tumor-bearing animals; this may be important in cardiovascular adaptation.

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.

The mechanism of the rate-dependent changes of the conducted action potential in rabbit ventricle

1989 ◽  
Vol 67 (7) ◽  
pp. 780-787 ◽  
Author(s):  
Elena Ruiz-Petrich ◽  
Normand Leblanc
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Outward Current ◽  
Transient Outward Current ◽  
Ca Current ◽  
Rate Dependent ◽  
Determinants Of Action ◽  
Frequency Of Stimulation ◽  
Potential Parameters

Blockers of the transient outward current (4-aminopyridine) and the Ca current (Co2+) as well as injection of polarizing current during the plateau were used to assess the role of these current systems as determinants of action potential duration at different pacing rates. Papillary muscles and ventricular trabecula were superfused with oxygenated Krebs solution at 33 °C and driven at a basic rate of 1 Hz. The effects of varying the frequency of stimulation between 0.1 and 4 Hz on action potential parameters were determined under control conditions and during exposure to 2 mM 4-aminopyridine, 1–3 mM CoCl2, or a mixture of 4-aminopyridine and CoCl2. The control relationship between action potential duration and pacing rate showed a maximum between 1 and 2 Hz. Under 4-aminopyridine, the plateau height and the action potential duration increased. The rate-dependent shortening of the action potential at frequencies below 1 Hz was reduced or abolished, and enhanced shortening was observed at rates above 1 Hz. Exposure to Co2+ reduced the action potential shortening at rates higher than 1 Hz. Both blockers, 4-aminopyridine and Co2+ were necessary to eliminate the rate-dependent changes of the action potential duration. Our results indicated that both the transient outward current and the inward calcium current determine the plateau height and duration for frequencies ≤2 Hz, whereas at higher rates, the Ca current plays a dominant role.Key words: action potential duration, stimulation rate, Ca current, transient outward current.

Modulation of electrical heterogeneity by compensated hypertrophy in rat left ventricle

1997 ◽  
Vol 272 (3) ◽  
pp. H1078-H1086 ◽  
Author(s):  
A. M. Gomez ◽  
J. P. Benitah ◽  
D. Henzel ◽  
A. Vinet ◽  
P. Lorente ◽  
...  
Keyword(s):  
Action Potential ◽  
Ventricular Myocytes ◽  
Regional Distribution ◽  
Outward Current ◽  
Left Ventricular ◽  
Transient Outward Current ◽  
Abdominal Aortic ◽  
Cell Current ◽  
Normal Rat

Modulation of the regional distribution of the action potential by left ventricular hypertrophy and the role of the L-type Ca2+ current (I(Ca)) and transient outward current (I(to)) in the action potential duration (APD) were investigated in normal and hypertrophied rat ventricular myocytes from the apex (A), septum (S) and left ventricular free wall (FW) by using whole cell current- and voltage-clamp techniques. Hypertrophy was induced by abdominal aortic constriction. In control cells, the APD measured at 20% repolarization (APD20) assumed the shortest values in the A and the longest in the S, whereas FW cells showed intermediate values. Hypertrophy significantly prolonged the APD20 and increased APD variability within the A and FW regions but did not modify the APD in S cells. Analysis of the APD, I(Ca), and I(to) at the instant of 20% repolarization in the same cell showed that in control cells the shortest APD20 was associated with a prominent I(to) in the A and FW, whereas the long APD20 was identified with a lower I(to) in S myocytes. Hypertrophy-induced prolongation ofAPD20 was associated with a reduction in the I(to) in the A and FW. Significant correlations could be established between the APD20 and the "net current," defined as the algebraic addition of I(to) and I(Ca) in the A and FW control groups but not in the control S or hypertrophied cells whatever their origin. Our results indicate that interregional APD heterogeneity is lost while intraregional APD variability is increased in the A and FW during the hypertrophic process. These effects are largely due to a change in the balance between the I(Ca) and I(to), which is a major contributing factor to the heterogeneity of the initial phase of repolarization in the normal rat ventricle.

Abstract 16953: Role of the Fast Transient Outward Current Ito,f in Shaping Action Potential Waveforms in Human iPSC-derived Cardiomyocytes

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Scott Marrus ◽  
Steven Springer ◽  
Rita Martinez ◽  
Edward Dranoff ◽  
Rebecca Mellor ◽  
...  
Keyword(s):  
Action Potential ◽  
Potassium Current ◽  
Ventricular Myocytes ◽  
Current Clamp ◽  
Transient Outward Potassium Current ◽  
Fast Transient ◽  
Human Ipsc ◽  
Outward Potassium Current ◽  
Upstroke Velocity

Abnormalities of a key repolarizing cardiac potassium current, the fast transient outward potassium current, I to,f , are associated with both heart failure and congenital arrhythmia syndromes. However, the precise role of I to,f in shaping action potential waveforms remains unclear. This study was designed to define the functional role of the fast transient outward potassium current, I to,f , in shaping action potentials in human iPSC-derived cardiomyocytes (iPSC-CMs). Most iPSC-CMs (29 of 43 cells) demonstrated spontaneous electrical activity, slow upstroke velocity (63±71 V/s), a wide range of action potential durations (APD90 = 860±722 ms) and heterogeneous action potential waveforms. Using dynamic current clamp, a modeled human ventricular inwardly rectifying K + current, I K1 , was introduced into iPSC-CMs, resulting in silencing of spontaneous activity, hyperpolarization of the resting membrane potential (RMP = -90±3 mV), increased peak upstroke velocity (dV/dt = 346±71 V/s) and decreased APD90 (420±211 ms) to values similar to those recorded in isolated adult human ventricular myocytes (RMP = -84±3 mV, dV/dt = 348±101 V/s and APD90 = 468±133 ms, all p>0.05). Importantly, a ventricular-like action potential waveform was observed in 25 of the 26 cells studied following the dynamic clamp addition of I K1 . Using these cells as a model of human ventricular myocytes, further dynamic current clamp experiments introduced a modeled human fast transient outward K + current, I to,f , and revealed that increasing in the amplitude of I to,f results in an increase in the phase 1 notch and a progressive shortening of the action potential duration in iPSC-CMs. Together, the experiments here demonstrate that combining human iPSC-CMs with the power of the dynamic current clamp technique to modulate directly and precisely the “expression” of individual ionic currents provides a novel and quantitative approach to defining the roles of specific ionic conductances in regulating the excitability of human cardiomyocytes.

Differences in outward currents between neonatal and adult rabbit ventricular cells

1994 ◽  
Vol 266 (3) ◽  
pp. H1184-H1194 ◽  
Author(s):  
J. Sanchez-Chapula ◽  
A. Elizalde ◽  
R. Navarro-Polanco ◽  
H. Barajas
Keyword(s):  
Action Potential ◽  
Papillary Muscle ◽  
Action Potential Duration ◽  
Outward Current ◽  
Stimulation Frequency ◽  
Transient Outward Current ◽  
Adult Rabbit ◽  
Outward Currents ◽  
Recovery From Inactivation ◽  
In Cells

In adult rabbit ventricular preparations, action potential duration is significantly increased when stimulation frequency is increased from 0.1 to 1.0 Hz. In neonatal preparations, a similar change in stimulation frequency produced no significant increase in action potential duration. To identify the ionic basis for this difference, we studied different outward currents in single myocytes from papillary muscle and from epicardial tissue of adult and neonatal rabbits. The densities of the outward currents in neonatal cells were about one-half of the current density in adult cells. The density of the voltage-activated transient outward current (I(to1)) was smaller in cells from papillary muscle than in cells from epicardium in adult and newborn rabbits. We found major differences in the kinetic behavior of I(to1) between adult and neonatal cells: 1) the rate of apparent inactivation was faster in neonatal cells, and 2) the recovery from inactivation was significantly faster in neonatal cells, with a time constant of 113 vs. 1,356 ms. We propose that this marked difference in the recovery from inactivation of I(to1) is the basis for the difference in frequency dependence of action potential duration.

Intracellular calcium activates a chloride current in canine ventricular myocytes

1994 ◽  
Vol 267 (5) ◽  
pp. H1984-H1995 ◽  
Author(s):  
A. C. Zygmunt
Keyword(s):  
Potassium Current ◽  
Ventricular Myocytes ◽  
Single Cells ◽  
Reversal Potential ◽  
Outward Current ◽  
Chloride Current ◽  
Disulfonic Acid ◽  
Transient Outward Current ◽  
Triggered Arrhythmias ◽  
Inward Currents

The contribution of chloride and potassium to the 4-aminopyridine (4-AP)-resistant transient outward current was investigated in dog cardiac myocytes. Whole cell currents were recorded at 37 degrees C in single cells dissociated from epicardial and midmyocardial regions of the canine ventricle. Sodium-calcium exchange current and voltage-dependent transient outward potassium current (IA) were blocked in sodium-free solutions containing 2 mM 4-AP; sodium channels were inactivated by the -50-mV holding potential. When patch pipettes contained 0.4–0.8 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, voltage-clamp steps over the range -20 to +50 mV activated an inward calcium current (ICa) and a Ca(2+)-activated chloride current [ICl(Ca)]. ICl(Ca) was blocked by 200 microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, 1 mM 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), or reduction of external chloride. Independent of the presence of potassium, the reversal potential of the SITS-sensitive current varied with extracellular chloride, as predicted for a chloride-selective conductance. The bell-shaped current-voltage relation of ICl(Ca) has a threshold of -20 mV and a peak at +40 mV. No evidence could be found for a Ca(2+)-activated potassium current or a Ca(2+)-activated nonspecific cation current under these conditions. ICl(Ca) contributed to oscillatory inward currents at diastolic potentials in cells superfused by isoproterenol and high Ca2+, suggesting a role for this current in triggered arrhythmias associated with delayed afterdepolarizations. In the normal heart, ICl(Ca) is likely to contribute to rate- and rhythm-dependent repolarization of the cardiac action potential.

Role of the Transient Outward Current in Regulating Mechanical Properties of Canine Ventricular Myocytes

2010 ◽  
Vol 21 (6) ◽  
pp. 697-703 ◽  
Author(s):  
MIN DONG ◽  
SUJUAN YAN ◽  
YAMEI CHEN ◽  
PAUL J. NIKLEWSKI ◽  
XIAOYIN SUN ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Transient Outward Current

Effects of thyroid hormone on action potential and repolarizing currents in rat ventricular myocytes

2000 ◽  
Vol 278 (2) ◽  
pp. E302-E307 ◽  
Author(s):  
Zhuo-Qian Sun ◽  
Kaie Ojamaa ◽  
William A. Coetzee ◽  
Michael Artman ◽  
Irwin Klein
Keyword(s):  
Action Potential ◽  
Cardiac Electrophysiology ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Mechanisms Of Action ◽  
Transient Outward Current ◽  
Prolonged Action ◽  
Electrophysiological Properties ◽  
Whole Cell Patch Clamp ◽  
Prolonged Action Potential Duration

Thyroid hormones play an important role in cardiac electrophysiology through both genomic and nongenomic mechanisms of action. The effects of triiodothyronine (T3) on the electrophysiological properties of ventricular myocytes isolated from euthyroid and hypothyroid rats were studied using whole cell patch clamp techniques. Hypothyroid ventricular myocytes showed significantly prolonged action potential duration (APD90) compared with euthyroid myocytes, APD90 of 151 ± 5 vs. 51 ± 8 ms, respectively. Treatment of hypothyroid ventricular myocytes with T3 (0.1 μM) for 5 min significantly shortened APD by 24% to 115 ± 10 ms. T3 similarly shortened APD in euthyroid ventricular myocytes, but only in the presence of 4-aminopyridine (4-AP), an inhibitor of the transient outward current ( I to), which prolonged the APD by threefold. Transient outward current ( I to) was not affected by the acute application of T3 to either euthyroid or hypothyroid myocytes; however, I to density was significantly reduced in hypothyroid compared with euthyroid ventricular myocytes.

Sign in / Sign up

Export Citation Format

Share Document