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.

Intracellular Ca transients in rat cardiac myocytes: role of Na-Ca exchange in excitation-contraction coupling

1990 ◽  
Vol 258 (5) ◽  
pp. C944-C954 ◽  
Author(s):  
D. M. Bers ◽  
W. J. Lederer ◽  
J. R. Berlin
Keyword(s):  
Voltage Clamp ◽  
Release Mechanism ◽  
Ca Current ◽  
Experimental Conditions ◽  
Release Process ◽  
Pipette Solution ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Intracellular Ca

Membrane current and intracellular Ca concentration ([Ca]i) transients were recorded from isolated rat ventricular myocytes under voltage-clamp control. The cells were dialyzed by the patch pipette solution, which contained the fluorescent Ca indicator indo-1 and 0.5 mM Na. Under these experimental conditions, Ca entry via Na-Ca exchange did not appear to be appreciable even in the absence of extracellular Na. Increasing the duration of voltage-clamp pulses from 5 to 80 ms produced [Ca]i transients of increasing amplitude, while the peak Ca current was not changed. This duration dependence of the [Ca]i transient was most demonstrable at more negative test potentials (e.g., -20 to -30 mV) and was not qualitatively modified by Na-free solutions. This latter result indicates that Ca extrusion by Na-Ca exchange is not responsible for the smaller [Ca]i transients observed when the membrane is repolarized after very brief depolarizations. Although the peak Ca current was not changed by increasing pulse duration, the integrated Ca current was increased. These observations are consistent with a Ca-release mechanism in cardiac excitation-contraction coupling in which 1) the Ca-release process can be modulated by membrane potential or 2) the Ca entering the cell via Ca channels has a preferential access [compared with Ca from the sarcoplasmic reticulum (SR)] to the site(s) that control SR Ca release. The role of Na-Ca exchange in the decline of [Ca]i during relaxation was also explored. Removal of extracellular Na (Nao) resulted in 20% slowing of the decline in [Ca]i during relaxation. From this, we conclude that the Na-Ca exchange competes with SR to remove Ca from the cytoplasm and that under our control conditions the exchanger may account for 20% of this decline. The Nao dependence of relaxation was reduced at more positive membrane potentials and increased by SR Ca loading.

The impact of ovariectomy on cardiac excitation-contraction coupling is mediated through cAMP/PKA-dependent mechanisms

2017 ◽  
Vol 111 ◽  
pp. 51-60 ◽  
Author(s):  
Randi J. Parks ◽  
Oleg Bogachev ◽  
Martin Mackasey ◽  
Gibanananda Ray ◽  
Robert A. Rose ◽  
...  
Keyword(s):  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Cardiac Excitation ◽  
The Impact

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

scholarly journals Dual Role of Functionally Intact Dyadic Junctions in Cardiac Excitation-Contraction Coupling

2015 ◽  
Vol 108 (2) ◽  
pp. 266a
Author(s):  
Prakash Subramanyam ◽  
Donald D. Chang ◽  
Henry M. Colecraft
Keyword(s):  
Dual Role ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Cardiac Excitation

1178Unsuspected role of the cardiac PKA type I in excitation-contraction coupling and in heart failure development

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Gandon-Renard ◽  
I Bedioune ◽  
S Karam ◽  
A Varin ◽  
P Lechene ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ex Vivo ◽  
Cardiac Contractility ◽  
Cardiac Contraction ◽  
Type I ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Contraction And Relaxation

Abstract The cAMP-dependent protein kinase (PKA) consists of two regulatory (R) and two catalytic (C) subunits and comprises two subtypes, PKAI and PKAII, defined by the nature of their regulatory subunits, RIα and RIIα respectively. Whereas PKAII is thought to play a key role in β-adrenergic (β-AR) regulation of cardiac contractility, the function of PKAI is unclear. To address this question, we generated mice with cardiomyocyte-specific and conditional invalidation of the RIα subunit of PKA. Tamoxifen injection in 8 weeks-old mice resulted in a >70% decrease in RIα protein without modification of other PKA subunits, which was associated with ∼2-fold increased basal PKA activity in RIα-KO mice (p<0.05, N=6/group). This translated into enhanced cardiac contraction and relaxation, as observed in vivo by increased fractional shortening and E-wave velocity (p<0.05, N=10/group) and ex vivo by increased LV pressure and maximal rate of contraction and relaxation (p<0.05, N=9/group). L-type Ca2+ current density was increased in ventricular myocytes from RIα-KO, and β-AR stimulation was decreased by ∼50% (p<0.05, n=38 cells for WT, and, n=40 for RIα-KO). Consistently, Ca2+ transients amplitude and relaxation kinetics were increased, along with increased occurrence of Ca2+ sparks and waves (p<0.05, n=44 cells for WT, and, n=50 for RIα KO). Phosphorylation of Ca2+ channels (CaV1.2), PLB, RyR2 and cMyBP-C at PKA sites was increased >2-fold (p<0.05, N=6/group) in RIα KO without modification of total protein expression. With age, these mice developed a congestive heart failure (HF) phenotype with massive hypertrophy and fibrosis which eventually led to death in 50% of RIα-KO mice at 50 weeks (versus 0% in WT, p<0.01). These results reveal a previously unsuspected role of PKA type I in cardiac excitation-contraction coupling and HF.

scholarly journals SPEG: a key regulator of cardiac calcium homeostasis

2020 ◽  
Author(s):  
Hannah Campbell ◽  
Yuriana Aguilar-Sanchez ◽  
Ann P Quick ◽  
Dobromir Dobrev ◽  
Xander H T Wehrens
Keyword(s):  
Human Disease ◽  
Striated Muscle ◽  
Genetic Diseases ◽  
Cardiac Contractility ◽  
Tubule Formation ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Membrane Complex ◽  
Cardiac Excitation

Abstract Proper cardiac Ca2+ homeostasis is essential for normal excitation–contraction coupling. Perturbations in cardiac Ca2+ handling through altered kinase activity has been implicated in altered cardiac contractility and arrhythmogenesis. Thus, a better understanding of cardiac Ca2+ handling regulation is vital for a better understanding of various human disease processes. ‘Striated muscle preferentially expressed protein kinase’ (SPEG) is a member of the myosin light chain kinase family that is key for normal cardiac function. Work within the last 5 years has revealed that SPEG has a crucial role in maintaining normal cardiac Ca2+ handling through maintenance of transverse tubule formation and phosphorylation of junctional membrane complex proteins. Additionally, SPEG has been causally impacted in human genetic diseases such as centronuclear myopathy and dilated cardiomyopathy as well as in common acquired cardiovascular disease such as heart failure and atrial fibrillation. Given the rapidly emerging role of SPEG as a key cardiac Ca2+ regulator, we here present this review in order to summarize recent findings regarding the mechanisms of SPEG regulation of cardiac excitation–contraction coupling in both physiology and human disease. A better understanding of the roles of SPEG will be important for a more complete comprehension of cardiac Ca2+ regulation in physiology and disease.

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