scholarly journals Metabolic Inhibition Induces Transient Increase of L-type Ca2+ Current in Human and Rat Cardiac Myocytes

2019 ◽  
Vol 20 (6) ◽  
pp. 1501 ◽  
Author(s):  
Rimantas Treinys ◽  
Giedrius Kanaporis ◽  
Rodolphe Fischmeister ◽  
Jonas Jurevičius
Keyword(s):  
Cardiac Myocytes ◽  
Early Phase ◽  
Metabolic Inhibition ◽  
Metabolic Inhibitors ◽  
Initial Increase ◽  
Adrenergic Stimulation ◽  
Patch Clamp Technique ◽  
Rat Cardiomyocytes ◽  
Wide Range ◽  
Rat Cardiac Myocytes

Metabolic inhibition is a common condition observed during ischemic heart disease and heart failure. It is usually accompanied by a reduction in L-type Ca2+ channel (LTCC) activity. In this study, however, we show that metabolic inhibition results in a biphasic effect on LTCC current (ICaL) in human and rat cardiac myocytes: an initial increase of ICaL is observed in the early phase of metabolic inhibition which is followed by the more classical and strong inhibition. We studied the mechanism of the initial increase of ICaL in cardiac myocytes during β-adrenergic stimulation by isoprenaline, a non-selective agonist of β-adrenergic receptors. The whole-cell patch–clamp technique was used to record the ICaL in single cardiac myocytes. The initial increase of ICaL was induced by a wide range of metabolic inhibitors (FCCP, 2,4-DNP, rotenone, antimycin A). In rat cardiomyocytes, the initial increase of ICaL was eliminated when the cells were pre-treated with thapsigargin leading to the depletion of Ca2+ from the sarcoplasmic reticulum (SR). Similar results were obtained when Ca2+ release from the SR was blocked with ryanodine. These data suggest that the increase of ICaL in the early phase of metabolic inhibition is due to a reduced calcium dependent inactivation (CDI) of LTCCs. This was further confirmed in human atrial myocytes where FCCP failed to induce the initial stimulation of ICaL when Ca2+ was replaced by Ba2+, eliminating CDI of LTCCs. We conclude that the initial increase in ICaL observed during the metabolic inhibition in human and rat cardiomyocytes is a consequence of an acute reduction of Ca2+ release from SR resulting in reduced CDI of LTCCs.

Abstract 1076: Conditional Fkbp12.6 Overexpression In Mouse Cardiac Myocytes Protects From Triggered Ventricular Arrhythmia Through Specific Alteration In Ec Coupling

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Barnabas Gellen ◽  
Ana-Maria Gomez ◽  
Khai Le Quang ◽  
Francois Briec ◽  
Laurent Vinet ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Antiarrhythmic Effect ◽  
Adrenergic Stimulation ◽  
Patch Clamp Technique ◽  
Ec Coupling ◽  
Before And After ◽  
Isolated Cardiac Myocytes ◽  
Pre Treatment ◽  
Specific Alteration ◽  
Ventricular Tachycardias

In cardiac myocytes, Ca2+ release from the sarcoplasmic reticulum (SR) into the cytoplasm via the ryanodine receptor (RyR2) activates cell contraction. During diastole, RyR2 are closed and prevent Ca2+ efflux from the SR. One of the major regulators of RyR2 function is FKBP12.6. Binding of FKBP12.6 stabilizes RyR2 in the closed formation in diastole and contributes to synchronized RyR2 opening in systole. Beta-adrenergic stimulation dissociates FKBP12.6 from RyR2, leading to diastolic Ca2+ leak that can trigger ventricular tachycardias (VT). We tested the hypothesis whether FKBP12.6 overexpression in the myocardium can reduce the susceptibility to VT in stress conditions. We developed a mouse model with conditional cardiac specific overexpression of FKBP12.6 using the Tet-Off system. Transgenic (TG) mice and controls (CT) were examined by echocardiography, PV-catheterization, ECG, and underwent intracardiac stimulation to trigger VT before and after pre-treatment with isoproterenol. In isolated cardiac myocytes, SR Ca2+ load, Ca2+ sparks and Ca2+ transient were measured using confocal microscopy, and L-type Ca2+ current was determined by the patch-clamp technique. Echocardiography, PV-catheterization and ECG recording did not reveal differences between Tg (n=11) and CT (n=13) mice. Burst pacing (figure 1) could induce TV in 4 of 24 controls and in 0 of 14 TG mice (n.s.). Following pre-treatment with isoproterenol, TV could be induced in 10 of 23 controls, but only in 1 of 14 TG animals (figure 2, p<0.05). In isolated myocytes, decreased Ca2+ spark frequency, increased Ca2+ spark size, unchanged SR Ca2+ load and decreased Ca2+ transient were observed in TG cells (n=19) as compared to controls (n=48, p<0.05). L-type Ca2+ channel current was found to be decreased in Tg myocytes (n=29 vs n=32, p<0.01). We conclude that myocardial FKBP12.6 overexpression has a protective effect against VT induced by rapid pacing after pretreatment with catecholamines. This antiarrhythmic effect is probably, at least in part, linked to decreased diastolic SR Ca2+ leak. Our results support the hypothesis that increased FKBP12.6 binding to RyR2 might represent a potential therapeutical target in the prevention and treatment of ventricular arrhythmias.

Properties of voltage-gated Ca2+ channels in rabbit ventricular myocytes expressing Ca2+ channel α1E cDNA

2001 ◽  
Vol 280 (1) ◽  
pp. C175-C182 ◽  
Author(s):  
Michihiro Tateyama ◽  
Shuqin Zong ◽  
Tsutomu Tanabe ◽  
Rikuo Ochi
Keyword(s):  
Cardiac Myocytes ◽  
Fluorescent Protein ◽  
Ventricular Myocytes ◽  
Foreign Gene ◽  
Adrenergic Stimulation ◽  
Patch Clamp Technique ◽  
Voltage Range ◽  
Whole Cell Patch Clamp ◽  
Green Fluorescent ◽  
Ca2 Channels

Using the whole-cell patch-clamp technique, we have studied the properties of α1ECa2+ channel transfected in cardiac myocytes. We have also investigated the effect of foreign gene expression on the intrinsic L-type current ( I Ca,L). Expression of green fluorescent protein significantly decreased the I Ca,L. By contrast, expression of α1E with β2b and α2/δ significantly increased the total Ca2+ current, and in these cells a Ca2+ antagonist, PN-200-110 (PN), only partially blocked the current. The remaining PN-resistant current was abolished by the application of a low concentration of Ni2+and was little affected by changing the charge carrier from Ca2+ to Ba2+ or by β-adrenergic stimulation. On the basis of its voltage range for activation, this channel was classified as a high-voltage activated channel. Thus the expression of α1E did not generate T-like current in cardiac myocytes. On the other hand, expression of α1E decreased I Ca,L and slowed the I Ca,L inactivation. This inactivation slowing was attenuated by the β2b coexpression, suggesting that the α1E may slow the inactivation of I Ca,L by scrambling with α1C for intrinsic auxiliary β.

Intracellular pH and Ca2+ homeostasis in the pH paradox of reperfusion injury to neonatal rat cardiac myocytes

1993 ◽  
Vol 265 (1) ◽  
pp. C129-C137 ◽  
Author(s):  
J. M. Bond ◽  
E. Chacon ◽  
B. Herman ◽  
J. J. Lemasters
Keyword(s):  
Reperfusion Injury ◽  
Cardiac Myocytes ◽  
Intracellular Ph ◽  
Ischemia Reperfusion ◽  
Atp Depletion ◽  
Neonatal Rat ◽  
Metabolic Inhibitors ◽  
Simulated Ischemia ◽  
Neonatal Rat Cardiac Myocytes ◽  
Rat Cardiac Myocytes

Ischemia is characterized by anoxia and a large decrease of tissue pH. After a critical period of ischemia, reperfusion precipitates irreversible injury. Previous work showed that reperfusion injury to cultured neonatal myocytes was precipitated by a rapid return to physiological pH, a "pH paradox" (Bond, J., B. Herman, and J. Lemasters. Biochem. Biophys. Res. Commun. 179: 798-803, 1991). The aim of this study was to measure intracellular pH (pHi) and cytosolic free Ca2+ during the pH paradox of reperfusion injury to cultured neonatal rat cardiac myocytes. pHi and free Ca2+ were measured by ratio imaging of 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein and fura 2 fluorescence. To simulate ATP depletion and acidosis of ischemia, myocytes were incubated with 20 mM 2-deoxyglucose plus 2.5 mM NaCN at pH 6.2. During simulated ischemia, pHi dropped to < 6.5 and subsequently remained constant. During this time, some blebbing but little hypercontraction occurred. After 3 or 4 h of simulated ischemia, inhibitors were removed and cells were incubated at pH 7.4 to simulate reperfusion. pHi began to increase, blebbing accelerated, and myocytes hypercontracted. As pHi increased, viability was lost. The same occurred if pH was increased but metabolic inhibitors were not removed. Monensin, a Na(+)-H+ ionophore, accelerated the increase of pH after reperfusion and hastened cell killing. Hypercontraction, blebbing, and loss of viability did not occur when inhibitors were removed at pH 6.2 or in the presence of dimethylamiloride, an inhibitor of Na(+)-H+ exchange. Protection was associated with maintenance of an acidotic pHi. Free Ca2+ progressively increased during simulated ischemia. After simulated reperfusion, free Ca2+ increased further.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Stimulation Regulates Na+/Ca2+Exchanger Expression in Rat Cardiac Myocytes

2000 ◽  
Vol 32 (4) ◽  
pp. 611-620 ◽  
Author(s):  
Kish L Golden ◽  
Q Ivy Fan ◽  
Bin Chen ◽  
Jun Ren ◽  
Jessica O»Connor ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Adrenergic Stimulation ◽  
Rat Cardiac Myocytes

scholarly journals NO donors potentiate the β‐adrenergic stimulation of I Ca,L and the muscarinic activation of I K,ACh in rat cardiac myocytes

2002 ◽  
Vol 540 (2) ◽  
pp. 411-424 ◽  
Author(s):  
Najah Abi‐Gerges ◽  
Gabor Szabo ◽  
Angela S. Otero ◽  
Rodolphe Fischmeister ◽  
Pierre‐François Méry
Keyword(s):  
Cardiac Myocytes ◽  
Adrenergic Stimulation ◽  
No Donors ◽  
Rat Cardiac Myocytes ◽  
Stimulation Of
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