scholarly journals Regulation of cardiac excitation–contraction coupling by action potential repolarization: role of the transient outward potassium current ( I to )

2003 ◽  
Vol 546 (1) ◽  
pp. 5-18 ◽  
Author(s):  
Rajan Sah ◽  
Rafael J. Ramirez ◽  
Gavin Y. Oudit ◽  
Dominica Gidrewicz ◽  
Maria G. Trivieri ◽  
...  
Keyword(s):  
Action Potential ◽  
Potassium Current ◽  
Transient Outward Potassium Current ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Cardiac Excitation ◽  
Outward Potassium Current ◽  
Action Potential Repolarization

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.

scholarly journals Mechanisms of transmurally varying myocyte electromechanics in an integrated computational model

2008 ◽  
Vol 366 (1879) ◽  
pp. 3361-3380 ◽  
Author(s):  
Stuart G Campbell ◽  
Sarah N Flaim ◽  
Chae H Leem ◽  
Andrew D McCulloch
Keyword(s):  
Potassium Current ◽  
Left Ventricular ◽  
Ventricular Wall ◽  
Mechanical Function ◽  
Transient Outward Potassium Current ◽  
Contraction Coupling ◽  
Coupling Characteristics ◽  
Outward Potassium Current ◽  
In Cells

The mechanical properties of myocardium vary across the transmural aspect of the left ventricular wall. Some of these functional heterogeneities may be related to differences in excitation–contraction coupling characteristics that have been observed in cells isolated from the epicardial, mid-myocardial and endocardial regions of the left ventricle of many species, including canine. Integrative models of coupled myocyte electromechanics are reviewed and used here to investigate sources of heterogeneous electromechanical behaviour in these cells. The simulations (i) illustrate a previously unrecognized role of the transient outward potassium current in mechanical function and (ii) suggest that there may also exist additional heterogeneities affecting crossbridge cycling rates in cells from different transmural regions.

scholarly journals Role of the transient outward potassium current in the genesis of early afterdepolarizations in cardiac cells

2012 ◽  
Vol 95 (3) ◽  
pp. 308-316 ◽  
Author(s):  
Zhenghang Zhao ◽  
Yuanfang Xie ◽  
Hairuo Wen ◽  
Dandan Xiao ◽  
Charelle Allen ◽  
...  
Keyword(s):  
Potassium Current ◽  
Cardiac Cells ◽  
Early Afterdepolarizations ◽  
Transient Outward Potassium Current ◽  
Outward Potassium Current

Cardiac excitation-contraction coupling: role of membrane potential in regulation of contraction

2001 ◽  
Vol 280 (5) ◽  
pp. H1928-H1944 ◽  
Author(s):  
Gregory R. Ferrier ◽  
Susan E. Howlett
Keyword(s):  
Membrane Potential ◽  
Regulatory Mechanism ◽  
Cardiac Contraction ◽  
Release Mechanism ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Regulation Of Contraction ◽  
Cardiac Excitation ◽  
The Impact

The steps that couple depolarization of the cardiac cell membrane to initiation of contraction remain controversial. Depolarization triggers a rise in intracellular free Ca2+ which activates contractile myofilaments. Most of this Ca2+ is released from the sarcoplasmic reticulum (SR). Two fundamentally different mechanisms have been proposed for SR Ca2+ release: Ca2+-induced Ca2+ release (CICR) and a voltage-sensitive release mechanism (VSRM). Both mechanisms operate in the same cell and may contribute to contraction. CICR couples the release of SR Ca2+ closely to the magnitude of the L-type Ca2+ current. In contrast, the VSRM is graded by membrane potential rather than Ca2+ current. The electrophysiological and pharmacological characteristics of the VSRM are strikingly different from CICR. Furthermore, the VSRM is strongly modulated by phosphorylation and provides a new regulatory mechanism for cardiac contraction. The VSRM is depressed in heart failure and may play an important role in contractile dysfunction. This review explores the operation and characteristics of the VSRM and CICR and discusses the impact of the VSRM on our understanding of cardiac excitation-contraction coupling.

Role of creatine kinase in cardiac excitation‐contraction coupling: studies in creatine kinase‐deficient mice

2002 ◽  
Vol 16 (7) ◽  
pp. 653-660 ◽  
Author(s):  
Bertrand Crozatier ◽  
Thierry Badoual ◽  
Ernest Boehm ◽  
Pierre‐Vladimir Ennezat ◽  
Thierry Guenoun ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Cardiac Excitation ◽  
Deficient Mice
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