The ERK pathway regulates Na+-HCO 3 − cotransport activity in adult rat cardiomyocytes

2002 ◽  
Vol 283 (5) ◽  
pp. H2102-H2109 ◽  
Author(s):  
Delphine Baetz ◽  
Robert S. Haworth ◽  
Metin Avkiran ◽  
Danielle Feuvray
Keyword(s):  
Ventricular Myocytes ◽  
Immunoblot Analysis ◽  
Erk Pathway ◽  
Ang Ii ◽  
Intracellular Acidification ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Erk Phosphorylation ◽  
Acid Load

The sarcolemmal Na+-HCO[Formula: see text] cotransporter (NBC) is stimulated by intracellular acidification and acts as an acid extruder. We examined the role of the ERK pathway of the MAPK cascade as a potential mediator of NBC activation by intracellular acidification in the presence and absence of angiotensin II (ANG II) in adult rat ventricular myocytes. Intracellular pH (pHi) was recorded with the use of seminaphthorhodafluor-1. The NH[Formula: see text]method was used to induce an intracellular acid load. NBC activation was significantly decreased with the ERK inhibitors PD-98059 and U-0126. NBC activity after acidification was increased in the presence of ANG II (pHi range of 6.75–7.00). ANG II plus PD-123319 (AT2 antagonist) still increased NBC activity, whereas ANG II plus losartan (AT1 antagonist) did not affect it. ERK phosphorylation (measured by immunoblot analysis) during intracellular acidification was increased by ANG II, an effect that was abolished by losartan and U-0126. In conclusion, the MAPK(ERK)-dependent pathway facilitates the rate of pHirecovery from acid load through NBC activity and is involved in the AT1 receptor-mediated stimulation of such activity by ANG II.

HCO 3 − -dependent alkalinizing transporter in adult rat ventricular myocytes: characterization and modulation

1997 ◽  
Vol 273 (6) ◽  
pp. H2596-H2603 ◽  
Author(s):  
Karine Le Prigent ◽  
Dominique Lagadic-Gossmann ◽  
Emmanuel Mongodin ◽  
Danielle Feuvray
Keyword(s):  
Ventricular Myocytes ◽  
Intracellular Acidification ◽  
Total Acid ◽  
Adult Rats ◽  
Adult Rat ◽  
Ventricular Cells ◽  
Intracellular Ca ◽  
Acid Load ◽  
Decreasing Ph ◽  
Intracellular Acid

The present work was designed to identify the [Formula: see text]-dependent alkalinizing carrier in ventricular myocytes of normal and diabetic adult rats and to determine to what extent this system contributes to acid-equivalent extrusion after an intracellular acidification. We also examined the possible influence of intracellular Ca2+([Formula: see text]) and glycolytic inhibition on the carrier activation. Intracellular pH (pHi) was recorded using seminaphthorhodafluor-1. The [Formula: see text] method was used to induce an intracellular acid load. Evidence is provided for the existence of a Cl−-independent Na+-[Formula: see text]cotransport contributing to pHirecovery from an intracellular acid load in ventricular cells of adult rats. Na+-[Formula: see text]cotransport accounts for 33% of the total acid-equivalent efflux ([Formula: see text]) from normal adult myocytes after intracellular acidification at pHi 6.75 in CO2/[Formula: see text]-buffered solution. In addition, the activity of this carrier, which is not affected either by decreasing [Formula: see text] or by inhibiting Ca2+/calmodulin protein kinase II, is downregulated by inhibition of glycolysis. Under pathophysiological conditions such as diabetes, although total[Formula: see text] was significantly decreased compared with normal myocytes,[Formula: see text] carried by Na+-[Formula: see text]cotransport remained unchanged. However, because of a decrease in Na+/H+exchange, the contribution of this carrier to total[Formula: see text] increased with decreasing pHi (i.e., under conditions that may be associated with an ischemic episode), reaching ∼58% of total[Formula: see text] at pHi 6.75 (vs. ∼33% in normal myocytes).

Arachidonic acid mediates dual effect of TNF-α on Ca2+ transients and contraction of adult rat cardiomyocytes

2002 ◽  
Vol 282 (6) ◽  
pp. C1339-C1347 ◽  
Author(s):  
Aïssata Amadou ◽  
Artur Nawrocki ◽  
Martin Best-Belpomme ◽  
Catherine Pavoine ◽  
Françoise Pecker
Keyword(s):  
Arachidonic Acid ◽  
Cyclooxygenase Inhibitors ◽  
High Dose ◽  
Negative Effects ◽  
Dual Effect ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Tnf Α ◽  
Biphasic Effect

Tumor necrosis factor (TNF)-α has a biphasic effect on heart contractility and stimulates phospholipase A2 (PLA2) in cardiomyocytes. Because arachidonic acid (AA) exerts a dual effect on intracellular Ca2+ concentration ([Ca2+]i) transients, we investigated the possible role of AA as a mediator of TNF-α on [Ca2+]i transients and contraction with electrically stimulated adult rat cardiac myocytes. At a low concentration (10 ng/ml) TNF-α produced a 40% increase in the amplitude of both [Ca2+]i transients and contraction within 40 min. At a high concentration (50 ng/ml) TNF-α evoked a biphasic effect comprising an initial positive effect peaking at 5 min, followed by a sustained negative effect leading to 50–40% decreases in [Ca2+]i transients and contraction after 30 min. Both the positive and negative effects of TNF-α were reproduced by AA and blocked by arachidonyltrifluoromethyl ketone (AACOCF3), an inhibitor of cytosolic PLA2. Lipoxygenase and cyclooxygenase inhibitors reproduced the high-dose effects of TNF-α and AA. The negative effects of TNF-α and AA were also reproduced by sphingosine and were abrogated by the ceramidase inhibitor n-oleoylethanolamine. These results point out the key role of the cytosolic PLA2/AA pathway in mediating the contractile effects of TNF-α.

Hyperthyroid adult rat cardiomyocytes. I. Nucleotide content, beta- and alpha-adrenoreceptors, and cAMP production

1989 ◽  
Vol 257 (5) ◽  
pp. C948-C956 ◽  
Author(s):  
C. M. Hohl ◽  
S. Wetzel ◽  
R. H. Fertel ◽  
D. K. Wimsatt ◽  
G. P. Brierley ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Adenine Nucleotide ◽  
Phosphodiesterase Inhibitor ◽  
Cardiac Cells ◽  
Beta Agonist ◽  
Camp Production ◽  
Adult Rats ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Half Maximal Effective Concentration

Ventricular myocytes isolated from the hypertrophied hearts of thyrotoxic adult rats have an increase in mean protein content per myocyte (6.3 +/- 0.2 vs. 4.4 +/- 0.2 ng) compared with euthyroid cells. Viability and adenine nucleotide profiles are similar in both populations, but NAD content of the hyperthyroid myocytes is depressed (4.9 +/- 0.2 vs. 5.5 +/- 0.2 nmol/mg for controls) and UTP is higher (1.2 +/- 0.09 vs. 0.9 +/- 0.04 nmol/mg). Binding of (-)-[125I]iodocyanopindolol to intact hyperthyroid myocytes is increased by 42% compared with controls, with no change in the dissociation constant (Kd). This elevation in beta-receptor number is correlated to enhanced beta-agonist-induced adenosine 3',5'-cyclic monophosphate (cAMP) production. The half-maximal effective concentration (EC50) for the euthyroid isoproterenol dose-response curve is 2.14 x 10(-7) M but is decreased to 2.51 x 10(-8) M in hyperthyroid cardiac cells. Basal adenylate cyclase activity is apparently not affected by thyroid hormones, since basal cAMP levels for both groups are identical (5 pmol/mg) and both rise roughly twofold in the presence of a phosphodiesterase inhibitor. Forskolin-induced cAMP production and cAMP-specific phosphodiesterase activity are similar as well. In contrast to beta-adrenergic response, there are no significant differences in alpha 1-antagonist [3H]prazosin binding parameters between hyperthyroid and euthyroid cardiomyocytes.

Protein kinase Cε and the antiadrenergic action of adenosine in rat ventricular myocytes

2004 ◽  
Vol 287 (4) ◽  
pp. H1721-H1729 ◽  
Author(s):  
Koji Miyazaki ◽  
Satoshi Komatsu ◽  
Mitsuo Ikebe ◽  
Richard A. Fenton ◽  
James G. Dobson
Keyword(s):  
Electrical Stimulation ◽  
Protein Kinase ◽  
Ventricular Myocytes ◽  
Adrenergic Agonist ◽  
Inhibitory Peptide ◽  
Rat Ventricular Myocytes ◽  
Adult Rat ◽  
Tubular System ◽  
Stimulation Of

Adenosine-induced antiadrenergic effects in the heart are mediated by adenosine A1 receptors (A1R). The role of PKCε in the antiadrenergic action of adenosine was explored with adult rat ventricular myocytes in which PKCε was overexpressed. Myocytes were transfected with a pEGFP-N1 vector in the presence or absence of a PKCε construct and compared with normal myocytes. The extent of myocyte shortening elicited by electrical stimulation of quiescent normal and transfected myocytes was recorded with video imaging. PKCε was found localized primarily in transverse tubules. The A1R agonist chlorocyclopentyladenosine (CCPA) at 1 μM rendered an enhanced localization of PKCε in the t-tubular system. The β-adrenergic agonist isoproterenol (Iso; 0.4 μM) elicited a 29–36% increase in myocyte shortening in all three groups. Although CCPA significantly reduced the Iso-produced increase in shortening in all three groups, the reduction caused by CCPA was greatest with PKCε overexpression. The CCPA reduction of the Iso-elicited shortening was eliminated in the presence of a PKCε inhibitory peptide. These results suggest that the translocation of PKCε to the t-tubular system plays an important role in A1R-mediated antiadrenergic actions in the heart.

Do β2-adrenergic receptors modulate Ca2+ in adult rat ventricular myocytes?

1998 ◽  
Vol 274 (4) ◽  
pp. H1308-H1314 ◽  
Author(s):  
Michael A. Laflamme ◽  
Peter L. Becker
Keyword(s):  
Pertussis Toxin ◽  
Calcium Homeostasis ◽  
Adrenergic Receptors ◽  
Calcium Current ◽  
Ventricular Myocytes ◽  
Camp Accumulation ◽  
Camp Production ◽  
Rat Ventricular Myocytes ◽  
Adult Rat

We examined the role of β2-adrenergic receptors (ARs) in modulating calcium homeostasis in rat ventricular myocytes. Zinterol (10 μM), an agonist with a 25-fold greater affinity for β2-ARs over β1-ARs, modestly enhanced L-type calcium current ( I Ca) magnitude by ∼30% and modestly accelerated the rate of Ca2+ concentration ([Ca2+]) decline (∼35%) but had little effect on the magnitude of the [Ca2+] transient (a nonsignificant 6% increase). However, 1 μM of the highly selective β1-AR antagonist CGP-20712A completely blocked the I Ca increase induced by 10 μM zinterol. Pretreatment of cells with pertussis toxin (PTX) did not alter I Ca enhancement by 10 μM zinterol, although it did abolish the ability of acetylcholine to block the forskolin-induced enhancement of I Ca. Zinterol (10 μM) approximately doubled adenosine 3′,5′-cyclic monophosphate (cAMP) accumulation, although one-half of this increase was blocked by CGP-20712A. In contrast, 1 μM of the nonselective β-agonist isoproterenol increased cAMP production 15-fold. Thus we found no evidence that activation of β2-ARs modulates calcium homeostasis in rat ventricular myocytes, even after treatment with PTX.

scholarly journals Role of epicardial mesothelial cells in the modification of phenotype and function of adult rat ventricular myocytes in primary coculture.

1992 ◽  
Vol 71 (1) ◽  
pp. 40-50 ◽  
Author(s):  
H Eid ◽  
D M Larson ◽  
J P Springhorn ◽  
M A Attawia ◽  
R C Nayak ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Mesothelial Cells ◽  
Rat Ventricular Myocytes ◽  
Adult Rat ◽  
And Function

scholarly journals Autophagy and protein kinase C are required for cardioprotection by sulfaphenazole

2010 ◽  
Vol 298 (2) ◽  
pp. H570-H579 ◽  
Author(s):  
Chengqun Huang ◽  
Wayne Liu ◽  
Cynthia N. Perry ◽  
Smadar Yitzhaki ◽  
Youngil Lee ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Enhanced Recovery ◽  
Ischemia Reperfusion ◽  
Dominant Negative ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Kinase C ◽  
Rat Hearts

Previously, we showed that sulfaphenazole (SUL), an antimicrobial agent that is a potent inhibitor of cytochrome P4502C9, is protective against ischemia-reperfusion (I/R) injury (Ref. 15 ). The mechanism, however, underlying this cardioprotection, is largely unknown. With evidence that activation of autophagy is protective against simulated I/R in HL-1 cells, and evidence that autophagy is upregulated in preconditioned hearts, we hypothesized that SUL-mediated cardioprotection might resemble ischemic preconditioning with respect to activation of protein kinase C and autophagy. We used the Langendorff model of global ischemia to assess the role of autophagy and protein kinase C in myocardial protection by SUL during I/R. We show that SUL enhanced recovery of function, reduced creatine kinase release, decreased infarct size, and induced autophagy. SUL also triggered PKC translocation, whereas inhibition of PKC with chelerythrine blocked the activation of autophagy in adult rat cardiomyocytes. In the Langendorff model, chelerythrine suppressed autophagy and abolished the protection mediated by SUL. SUL increased autophagy in adult rat cardiomyocytes infected with GFP-LC3 adenovirus, in isolated perfused rat hearts, and in mCherry-LC3 transgenic mice. To establish the role of autophagy in cardioprotection, we used the cell-permeable dominant-negative inhibitor of autophagy, Tat-Atg5K130R. Autophagy and cardioprotection were abolished in rat hearts perfused with recombinant Tat-Atg5K130R. Taken together, these studies indicate that cardioprotection mediated by SUL involves a PKC-dependent induction of autophagy. The findings suggest that autophagy may be a fundamental process that enhances the heart's tolerance to ischemia.

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