scholarly journals Effect of carvedilol on atrial excitation-contraction coupling, Ca2+ release, and arrhythmogenicity

2020 ◽  
Vol 318 (5) ◽  
pp. H1245-H1255
Author(s):  
E. Martinez-Hernandez ◽  
L. A. Blatter
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Antiarrhythmic Effect ◽  
Calcium Currents ◽  
Ion Currents ◽  
Atrial Myocytes ◽  
Release Channel ◽  
Contraction Coupling ◽  
Β Blocker ◽  
Atrial Excitation ◽  
Antiarrhythmic Effects

Here we show that the clinically widely used β-blocker carvedilol has profound effects on Ca2+ signaling and ion currents, but also antiarrhythmic effects in adult atrial myocytes. Carvedilol inhibits sodium and calcium currents and leads to failure of ECC but also prevents spontaneous Ca2+ release from cellular sarcoplasmic reticulum (SR) Ca2+ stores in form of arrhythmogenic Ca2+ waves. The antiarrhythmic effect occurs by carvedilol acting directly on the SR ryanodine receptor Ca2+ release channel.

scholarly journals Effects of mitochondrial uncoupling on Ca2+ signaling during excitation-contraction coupling in atrial myocytes

2013 ◽  
Vol 304 (7) ◽  
pp. H983-H993 ◽  
Author(s):  
Aleksey V. Zima ◽  
Malikarjuna R. Pabbidi ◽  
Stephen L. Lipsius ◽  
Lothar A. Blatter
Keyword(s):  
Ion Homeostasis ◽  
Inhibitory Effect ◽  
Partial Recovery ◽  
Atrial Myocytes ◽  
Mitochondrial Uncoupling ◽  
Release Channel ◽  
Excitation Contraction Coupling ◽  
Atp Production ◽  
Contraction Coupling ◽  
Reverse Mode

Mitochondria play an important role in intracellular Ca2+ concentration ([Ca2+]i) regulation in the heart. We studied sarcoplasmic reticulum (SR) Ca2+ release in cat atrial myocytes during depolarization of mitochondrial membrane potential (ΔΨm) induced by the protonophore FCCP. FCCP caused an initial decrease of action potential-induced Ca2+ transient amplitude and frequency of spontaneous Ca2+ waves followed by partial recovery despite partially depleted SR Ca2+ stores. In the presence of oligomycin, FCCP only exerted a stimulatory effect on Ca2+ transients and Ca2+ wave frequency, suggesting that the inhibitory effect of FCCP was mediated by ATP consumption through reverse-mode operation of mitochondrial F1F0-ATPase. ΔΨm depolarization was accompanied by cytosolic acidification, increases of diastolic [Ca2+]i, intracellular Na+ concentration ([Na+]i), and intracellular Mg2+ concentration ([Mg2+]i), and a decrease of intracellular ATP concentration ([ATP]i); however, glycolytic ATP production partially compensated for the exhaustion of mitochondrial ATP supplies. In conclusion, the initial inhibition of Ca2+ transients and waves resulted from suppression of ryanodine receptor SR Ca2+ release channel activity by a decrease in [ATP], an increase of [Mg2+]i, and cytoplasmic acidification. The later stimulation resulted from reduced mitochondrial Ca2+ buffering and cytosolic Na+ and Ca2+ accumulation, leading to enhanced Ca2+-induced Ca2+ release and spontaneous Ca2+ release in the form of Ca2+ waves. ΔΨm depolarization and the ensuing consequences of mitochondrial uncoupling observed here (intracellular acidification, decrease of [ATP]i, increase of [Na+]i and [Mg2+]i, and Ca2+ overload) are hallmarks of ischemia. These findings may therefore provide insight into the consequences of mitochondrial uncoupling for ion homeostasis, SR Ca2+ release, and excitation-contraction coupling in ischemia at the cellular and subcellular level.

Lactate inhibits Ca2+-activated Ca2+-channel activity from skeletal muscle sarcoplasmic reticulum

1997 ◽  
Vol 82 (2) ◽  
pp. 447-452 ◽  
Author(s):  
Terence G. Favero ◽  
, Anthony C. Zable ◽  
, David Colter ◽  
Jonathan J. Abramson
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Single Channel ◽  
Channel Activity ◽  
Release Channel ◽  
Muscle Lactate ◽  
Tension Development ◽  
Contraction Coupling ◽  
Single Channel Activity ◽  
High Concentrations

Favero, Terence G., Anthony C. Zable, David Colter, and Jonathan J. Abramson. Lactate inhibits Ca2+-activated Ca2+-channel activity from skeletal muscle sarcoplasmic reticulum. J. Appl. Physiol. 82(2): 447–452, 1997.—Sarcoplasmic reticulum (SR) Ca2+-release channel function is modified by ligands that are generated during about of exercise. We have examined the effects of lactate on Ca2+- and caffeine-stimulated Ca2+ release, [3H]ryanodine binding, and single Ca2+-release channel activity of SR isolated from rabbit white skeletal muscle. Lactate, at concentrations from 10 to 30 mM, inhibited Ca2+- and caffeine-stimulated [3H]ryanodine binding to and inhibited Ca2+- and caffeine-stimulated Ca2+ release from SR vesicles. Lactate also inhibited caffeine activation of single-channel activity in bilayer reconstitution experiments. These findings suggest that intense muscle activity, which generates high concentrations of lactate, will disrupt excitation-contraction coupling. This may lead to decreases in Ca2+ transients promoting a decline in tension development and contribute to muscle fatigue.

Calmodulin and Excitation-Contraction Coupling

Physiology ◽  
2000 ◽  
Vol 15 (6) ◽  
pp. 281-284 ◽  
Author(s):  
Susan L. Hamilton ◽  
Irina Serysheva ◽  
Gale M. Strasburg
Keyword(s):  
Skeletal Muscle ◽  
Ion Channels ◽  
Sarcoplasmic Reticulum ◽  
Release Channel ◽  
Excitation Contraction Coupling ◽  
Transverse Tubule ◽  
Contraction Coupling ◽  
Voltage Dependent ◽  
Important Regulator ◽  
Precise Role

Excitation-contraction coupling in cardiac and skeletal muscle involves the transverse-tubule voltage-dependent Ca2+ channel and the sarcoplasmic reticulum Ca2+ release channel. Both of these ion channels bind and are modulated by calmodulin in both its Ca2+-bound and Ca2+-free forms. Calmodulin is, therefore, potentially an important regulator of excitation-contraction coupling. Its precise role, however, has not yet been defined.

Different Compartments of Sarcoplasmic Reticulum Participate in the Excitation-Contraction Coupling Process in Human Atrial Myocytes

1997 ◽  
Vol 80 (3) ◽  
pp. 345-353 ◽  
Author(s):  
Stephane N. Hatem ◽  
Agnes Benardeau ◽  
Catherine Rucker-Martin ◽  
Isabelle Marty ◽  
Patricia de Chamisso ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Atrial Myocytes ◽  
Excitation Contraction Coupling ◽  
Human Atrial Myocytes ◽  
Coupling Process ◽  
Contraction Coupling

Single cardiac sarcoplasmic reticulum Ca2+-release channel: activation by caffeine

1989 ◽  
Vol 256 (2) ◽  
pp. H328-H333 ◽  
Author(s):  
E. Rousseau ◽  
G. Meissner
Keyword(s):  
Steady State ◽  
Sarcoplasmic Reticulum ◽  
Lipid Bilayers ◽  
Single Channel ◽  
Ruthenium Red ◽  
Planar Lipid Bilayers ◽  
Release Channel ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Channel Activation ◽  
Contraction Coupling

Caffeine is thought to affect excitation-contraction coupling in cardiac muscle by activating the sarcoplasmic reticulum (SR) Ca2+-release channel. The effect of caffeine at the single channel level was studied by incorporating canine cardiac SR vesicles into planar lipid bilayers. Cardiac Ca2+-release channels were activated in a steady-state manner by millimolar cis-caffeine and displayed a unitary conductance (77 pS in 50 mM Ca2+ trans) similar to that previously observed for the Ca2+-activated cardiac channel. The caffeine-activated channel was moderately sensitive to the voltage applied across the bilayer, was sensitive to further activation by ATP, and was inhibited by Mg2+ and ruthenium red. Kinetic analysis showed that at low Ca2+ concentration, caffeine activated the channel by increasing the frequency and the duration of open events.

scholarly journals Complex interactions between skeletal muscle ryanodine receptor and dihydropyridine receptor proteins

1998 ◽  
Vol 76 (5) ◽  
pp. 681-694 ◽  
Author(s):  
Peng Leong ◽  
David H MacLennan
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Ryanodine Receptor ◽  
Dihydropyridine Receptor ◽  
Release Channel ◽  
Excitation Contraction Coupling ◽  
Receptor Proteins ◽  
Contraction Coupling ◽  
Experimental Systems ◽  
Complex Interactions

Evidence for functional interactions between the Ca2+ release channel in the skeletal muscle sarcoplasmic reticulum (the ryanodine receptor) and the L-type Ca2+ channel in the sarcolemma (the dihydropyridine receptor), leading to excitation-contraction coupling, is reviewed and experimental systems used to identify candidate sites of interaction are outlined.Key words: sarcoplasmic reticulum, excitation-contraction coupling.

Ryanodine modifies conductance and gating behavior of single Ca2+ release channel

1987 ◽  
Vol 253 (3) ◽  
pp. C364-C368 ◽  
Author(s):  
E. Rousseau ◽  
J. S. Smith ◽  
G. Meissner
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Muscle ◽  
Lipid Bilayers ◽  
Single Channel ◽  
Ruthenium Red ◽  
Planar Lipid Bilayers ◽  
Open Probability ◽  
Release Channel ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling

Ryanodine affects excitation-contraction coupling in skeletal and cardiac muscle by specifically interacting with the sarcoplasmic reticulum (SR) Ca2+ release channel. The effect of the drug at the single channel level was studied by incorporating skeletal and cardiac SR vesicles into planar lipid bilayers. The two channels were activated by micromolar free Ca2+ and millimolar ATP and inhibited by Mg2+ and ruthenium red. Addition of micromolar concentrations of ryanodine decreased about twofold the unit conductance of the Ca2+- and ATP-activated skeletal and cardiac channels. A second effect of ryanodine was to increase the open probability (Po) of the channels in such a way that Po was close to unity under a variety of activating and inactivating conditions. The effects of ryanodine were long lasting in that removal of ryanodine by perfusion did not return the channels into their fully conducting state.

Metabolic end products inhibit sarcoplasmic reticulum Ca2+ release and [3H]ryanodine binding

1995 ◽  
Vol 78 (5) ◽  
pp. 1665-1672 ◽  
Author(s):  
T. G. Favero ◽  
A. C. Zable ◽  
M. B. Bowman ◽  
A. Thompson ◽  
J. J. Abramson
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Single Channel ◽  
Oxygen Species ◽  
Channel Activity ◽  
Open Probability ◽  
Release Channel ◽  
Tension Development ◽  
Contraction Coupling ◽  
End Products ◽  
Decreasing Ph

Sarcoplasmic reticulum (SR) Ca2+ release channel function is modified by ligands (Mg2+, Ca2+, ATP, and H+) that are generated during a bout of exercise. We have examined the effects of changing intracellular metabolites on Ca2+ release, [3H]ryanodine binding, and single-Ca2+ release channel activity of SR isolated from white rabbit skeletal muscle. Increasing Mg2+ (from 0 to 4 mM) and decreasing pH (7.1–6.5) inhibited SR Ca2+ release and [3H]-ryanodine binding. In addition, increasing lactate concentrations from 2 to 20 mM inhibited [3H]ryanodine binding to SR vesicles, inhibited SR Ca2+ release, and decreased the single-channel open probability. These findings suggest that intracellular modifications that disrupt excitation-contraction coupling and decrease Ca2+ transients will promote a decline in tension development and contribute to muscle fatigue. In addition, we show that hydrogen peroxide induces Ca2+ release and increases [3H]ryanodine binding to its receptor, suggesting that reactive oxygen species produced during exercise may compromise muscle function by altering the normal gating of the SR Ca2+ release channel.

scholarly journals Dantrolene suppresses spontaneous Ca2+ release without altering excitation-contraction coupling in cardiomyocytes of aged mice

2014 ◽  
Vol 307 (6) ◽  
pp. H818-H829 ◽  
Author(s):  
Timothy L. Domeier ◽  
Cale J. Roberts ◽  
Anne K. Gibson ◽  
Laurin M. Hanft ◽  
Kerry S. McDonald ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Dysfunction ◽  
Wave Amplitude ◽  
Left Ventricular ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Aged Mice ◽  
Cell Shortening ◽  
Antiarrhythmic Effects ◽  
Young Mice

Cardiac dysfunction in the aged heart reflects abnormalities in cardiomyocyte Ca2+ homeostasis including altered Ca2+ cycling through the sarcoplasmic reticulum (SR). The ryanodine receptor antagonist dantrolene exerts antiarrhythmic effects by preventing spontaneous diastolic Ca2+ release from the SR. We tested the hypothesis that dantrolene prevents spontaneous Ca2+ release without altering excitation-contraction coupling in aged myocardium. Left ventricular cardiomyocytes isolated from young (3 to 4 mo) and aged (24–26 mo) C57BL/6 mice were loaded with the Ca2+ indicator fluo-4. Amplitudes of action potential-induced Ca2+ transients at 1-Hz pacing were similar between young and aged mice, yet cell shortening was impaired in aged mice. Isoproterenol (1 μM) increased Ca2+ transient amplitude and cell shortening to identical levels in young and aged; dantrolene (1 μM) had no effect on Ca2+ transients or cell shortening during pacing. Under Ca2+ overload conditions induced with 10 mM extracellular Ca2+ concentration, spontaneous Ca2+ waves were of diminished amplitude and associated with lower SR Ca2+ content in aged versus young mice. Despite no effect in young mice, dantrolene increased SR Ca2+ content and Ca2+ wave amplitude in aged mice. In the presence of isoproterenol following rest from 1-Hz pacing, Ca2+ spark frequency was elevated in aged mice, yet the time to spontaneous Ca2+ wave was similar between young and aged mice; dantrolene decreased Ca2+ spark frequency and prolonged the time to Ca2+ wave onset in aged mice with no effect in young mice. Thus dantrolene attenuates diastolic Ca2+ release in the aged murine heart that may prove useful in preventing cardiac dysfunction.

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