DIDS-sensitive pHi regulation in single rat cardiac myocytes in nominally HCO3-free conditions.


:The fluorescent dye 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) was used to measure pHi in the spontaneously hypertensive rat (SHR) and in normal rat cardiac myocytes under nominally HCO3-free (20 mmol/L HEPES-buffered) conditions. When only the Na-H exchanger was blocked, the intrinsic buffering power (beta i) in SHR myocytes was significantly higher than when both the Na-H exchanger and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)-sensitive pHi regulators (the Na-HCO3 cotransporter and the Cl-HCO3 exchanger) were blocked. Similar low values for beta i were also found for normal rat myocytes in Na(+)-free conditions. In Cl(-)-free solution under nominally HCO3-free conditions, in both normal and SHR myocytes, the pHi slowly alkalinized (by 0.16 +/- 0.02 and 0.11 +/- 0.02 pH units, respectively); this alkalinization was also DIDS sensitive. The reacidification during NH4+ perfusion was inhibited 30.2 +/- 7.4% by DIDS. In addition, in the nominal absence of HCO3-, 100 mumol/L ATP acidified the pHi in both normal and SHR myocytes (by 0.21 +/- 0.03 and 0.33 +/- 0.03 pH units, respectively); this acidification was totally inhibited by 0.1 mmol/L DIDS. It has been shown, in rat cardiac myocytes, that ATP acidifies the pHi by 0.35 pH unit via stimulation of a DIDS-sensitive Cl-HCO3 exchanger in HCO3-containing solutions. Finally, we have shown, in normal cardiac myocytes, that two potent Na-H exchanger blockers, N-5-ethylisopropyl amiloride (EIPA) and N-5-methyl-N-isobutyl amiloride (MIA), only partially inhibited the pHi recovery from internal acidosis under nominally bicarbonate-free conditions. When DIDS was added at the same time as EIPA, pHi recovery from an internal acid loading was completely inhibited. Our results clearly demonstrate that in both normal and SHR cardiac myocytes, bicarbonate-dependent pHi regulators can be significantly activated under resting or acidified pHi in HEPES-buffered medium, probably because of the cellular production of CO2. The contribution of these bicarbonate-dependent pHi regulators, ie, the Na-HCO3 cotransporter and the Cl-HCO3 exchanger, cannot therefore be ignored even under nominally HCO3-free conditions.


Circ Res


Circulation research


Wu ML,Tsai ML,Tseng YZ




Has Abstract


1994-07-01 00:00:00












  • Endocardial versus epicardial differences of intracellular free calcium under normal and ischemic conditions in perfused rat hearts.

    abstract::Transmural heterogeneity of myocardial metabolism and function are present in the left ventricle under normal and ischemic conditions. To determine if endocardial versus epicardial differences of [Ca2+]i are also present, perfused rat heart studies using indo-1 fluorescence as an index of [Ca2+]i were performed in the...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Figueredo VM,Brandes R,Weiner MW,Massie BM,Camacho SA

    更新日期:1993-05-01 00:00:00

  • Cardiac-specific deletion of mkk4 reveals its role in pathological hypertrophic remodeling but not in physiological cardiac growth.

    abstract::Mitogen-activated protein kinase kinase (MKK)4 is a critical member of the mitogen-activated protein kinase family. It is able to activate the c-Jun NH(2)-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase in response to environmental stresses. JNK and p38 are strongly implicated in pathological ca...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Liu W,Zi M,Jin J,Prehar S,Oceandy D,Kimura TE,Lei M,Neyses L,Weston AH,Cartwright EJ,Wang X

    更新日期:2009-04-10 00:00:00

  • Peroxisome proliferator-activated receptor alpha induces NADPH oxidase activity in macrophages, leading to the generation of LDL with PPAR-alpha activation properties.

    abstract::Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors controlling lipid and glucose metabolism as well as inflammation. PPARs are expressed in macrophages, cells that also generate reactive oxygen species (ROS). In this study, we investigated whether PPARs regulate ROS production in macrophages. Di...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Teissier E,Nohara A,Chinetti G,Paumelle R,Cariou B,Fruchart JC,Brandes RP,Shah A,Staels B

    更新日期:2004-12-10 00:00:00

  • Hypoxia and hypoxia/reoxygenation activate Raf-1, mitogen-activated protein kinase kinase, mitogen-activated protein kinases, and S6 kinase in cultured rat cardiac myocytes.

    abstract::In response to hypoxia and reoxygenation, mammalian cells are known to express a variety of genes to adapt to these external stresses or lead to further cell damage. We investigated the intracellular signaling cascades in cultured rat cardiac myocytes subjected to hypoxia followed by reoxygenation (hypoxia/reoxygenati...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Seko Y,Tobe K,Ueki K,Kadowaki T,Yazaki Y

    更新日期:1996-01-01 00:00:00

  • Hypertension, transmural pressure, and vascular smooth muscle response in rats.

    abstract::The effect of transmural pressure on the responsiveness of vascular smooth muscle was studied using rats with chronic occlusion of one external iliac artery. The arterial pressure in the occluded leg was reduced to approximately half of that in the contralateral unoccluded leg. Helical strips from the low- and high-pr...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Hansen TR,Bohr DF

    更新日期:1975-05-01 00:00:00

  • Increased thromboxane biosynthesis during coronary thrombolysis. Evidence that platelet activation and thromboxane A2 modulate the response to tissue-type plasminogen activator in vivo.

    abstract::Platelet activation is markedly increased during coronary thrombolysis and limits the response to thrombolytic therapy. A possible mediator of platelet activation in this setting is thromboxane (TX) A2, a potent platelet agonist formed in greatly increased amounts during coronary thrombolysis in man. To address this h...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Fitzgerald DJ,Wright F,FitzGerald GA

    更新日期:1989-07-01 00:00:00

  • Ca(2+) transients and Ca(2+) waves in purkinje cells : role in action potential initiation.

    abstract::Purkinje cells contain sarcoplasmic reticulum (SR) directly under the surface membrane, are devoid of t-tubuli, and are packed with myofibrils surrounded by central SR. Several studies have reported that electrical excitation induces a biphasic Ca(2+) transient in Purkinje fiber bundles. We determined the nature of th...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Boyden PA,Pu J,Pinto J,Keurs HE

    更新日期:2000-03-03 00:00:00

  • Diminished Ca2+ sensitivity of skinned cardiac muscle contractility coincident with troponin T-band shifts in the diabetic rat.

    abstract::We have measured the apparent Ca2+ sensitivities of force development in skinned cardiac trabeculae at different sarcome lengths together with shifts in troponin (Tn) T subunits on specimens from the same hearts and drawn insights into the pathogenesis of myocardial dysfunction in the diabetic rat. The Ca(2+)-force re...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Akella AB,Ding XL,Cheng R,Gulati J

    更新日期:1995-04-01 00:00:00

  • Expression of beta-arrestins and beta-adrenergic receptor kinases in the failing human heart.

    abstract::The beta-adrenergic receptor system of the failing human heart is markedly desensitized. We have recently postulated that this desensitization may in part be caused by an increase in beta-adrenergic receptor kinase (beta ARK) expression. beta ARK is thought to effect desensitization by acting in concert with an inhibi...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Ungerer M,Parruti G,Böhm M,Puzicha M,DeBlasi A,Erdmann E,Lohse MJ

    更新日期:1994-02-01 00:00:00

  • Molecular composition of 4-aminopyridine-sensitive voltage-gated K(+) channels of vascular smooth muscle.

    abstract::Voltage-gated K(+) channels (Kv) play a critical role in regulating arterial tone by modulating the membrane potential of vascular smooth muscle cells. Our previous work demonstrated that the dominant 4-aminopyridine (4-AP)-sensitive, delayed rectifier Kv current of rabbit portal vein (RPV) myocytes demonstrates simil...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Thorneloe KS,Chen TT,Kerr PM,Grier EF,Horowitz B,Cole WC,Walsh MP

    更新日期:2001-11-23 00:00:00

  • Spatial heterogeneity of endothelial phenotypes correlates with side-specific vulnerability to calcification in normal porcine aortic valves.

    abstract::Calcific aortic valve sclerosis involves inflammatory processes and occurs preferentially on the aortic side of endothelialized valve leaflets. Although the endothelium is recognized to play critical roles in focal vascular sclerosis, the contributions of valvular endothelial phenotypes to aortic valve sclerosis and s...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Simmons CA,Grant GR,Manduchi E,Davies PF

    更新日期:2005-04-15 00:00:00

  • Identification of myocardial and vascular precursor cells in human and mouse epicardium.

    abstract::During cardiac development, the epicardium is the source of multipotent mesenchymal cells, which give rise to endothelial and smooth muscle cells in coronary vessels and also, possibly, to cardiomyocytes. The aim of the present study was to determine whether stem cells are retained in the adult human and murine epicar...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Limana F,Zacheo A,Mocini D,Mangoni A,Borsellino G,Diamantini A,De Mori R,Battistini L,Vigna E,Santini M,Loiaconi V,Pompilio G,Germani A,Capogrossi MC

    更新日期:2007-12-07 00:00:00

  • Regulation of oxygen distribution in tissues by endothelial nitric oxide.

    abstract::Nitric oxide (NO) decreases cellular oxygen (O(2)) consumption by competitively inhibiting cytochrome c oxidase. Here, we show that endogenously released endothelial NO, either basal or stimulated, can modulate O(2) consumption both throughout the thickness of conductance vessels and in the microcirculation. Furthermo...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Victor VM,Nuñez C,D'Ocón P,Taylor CT,Esplugues JV,Moncada S

    更新日期:2009-05-22 00:00:00

  • Heparin disrupts the CXCR4/SDF-1 axis and impairs the functional capacity of bone marrow-derived mononuclear cells used for cardiovascular repair.

    abstract:RATIONALE:Cell therapy is a promising option for the treatment of acute or chronic myocardial ischemia. The intracoronary infusion of cells imposes the potential risk of cell clotting, which may be prevented by the addition of anticoagulants. However, a comprehensive analysis of the effects of anticoagulants on the fun...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Seeger FH,Rasper T,Fischer A,Muhly-Reinholz M,Hergenreider E,Leistner DM,Sommer K,Manavski Y,Henschler R,Chavakis E,Assmus B,Zeiher AM,Dimmeler S

    更新日期:2012-09-14 00:00:00

  • Relationship between changes in left ventricular bipolar electrograms and regional myocardial blood flow during acute coronary artery occlusion in the dog.

    abstract::The purpose of this study was to determine whether a quantitative relationship existed between a reduction in regional myocardial blood flow, measured by radiolabeled microspheres, and the degree and type of changes in myocardial activation recorded in bipolar left ventricular subepicardial and subendocardial electrog...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Ruffy R,Lovelace DE,Mueller TM,Knoebel SB,Zipes DP

    更新日期:1979-12-01 00:00:00

  • Expression of slow skeletal troponin I in adult mouse heart helps to maintain the left ventricular systolic function during respiratory hypercapnia.

    abstract::Compared with the adult, neonatal heart muscle is less sensitive to deactivation by acidic pH. We hypothesized that expression of slow skeletal troponin I (ssTnI), the embryonic isoform, in adult heart would help maintain left ventricular (LV) systolic function during respiratory hypercapnia. We assessed LV function b...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Urboniene D,Dias FA,Peña JR,Walker LA,Solaro RJ,Wolska BM

    更新日期:2005-07-08 00:00:00

  • Dephosphorylation and intracellular redistribution of ventricular connexin43 during electrical uncoupling induced by ischemia.

    abstract::Electrical uncoupling at gap junctions during acute myocardial ischemia contributes to conduction abnormalities and reentrant arrhythmias. Increased levels of intracellular Ca(2+) and H(+) and accumulation of amphipathic lipid metabolites during ischemia promote uncoupling, but other mechanisms may play a role. We tes...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Beardslee MA,Lerner DL,Tadros PN,Laing JG,Beyer EC,Yamada KA,Kléber AG,Schuessler RB,Saffitz JE

    更新日期:2000-10-13 00:00:00

  • Creatine phosphate consumption and the actomyosin crossbridge cycle in cardiac muscles.

    abstract::To investigate the regulation of the actomyosin crossbridge cycle in cardiac muscles, the effects of ATP, ADP, Pi, and creatine phosphate (CP) on the rate of force redevelopment (ktr) were measured. We report that CP is a primary determinant in controlling the actomyosin crossbridge cycling kinetics of cardiac muscles...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Ogut O,Brozovich FV

    更新日期:2003-07-11 00:00:00

  • Superoxide mediates the actions of angiotensin II in the central nervous system.

    abstract::Angiotensin II (Ang II) has profound effects in the central nervous system (CNS), including promotion of thirst, regulation of vasopressin secretion, and modulation of sympathetic outflow. Despite its importance in cardiovascular and volume homeostasis, angiotensinergic mechanisms are incompletely understood in the CN...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Zimmerman MC,Lazartigues E,Lang JA,Sinnayah P,Ahmad IM,Spitz DR,Davisson RL

    更新日期:2002-11-29 00:00:00

  • Ionic bases for electrophysiological distinctions among epicardial, midmyocardial, and endocardial myocytes from the free wall of the canine left ventricle.

    abstract::Recent studies from our laboratory involving syncytial preparations have delineated electrophysiological distinctions between epicardium, endocardium, and a unique population of cells in the deep subepicardial to midmyocardial layers (M region) of the canine ventricle. In the present study, we used standard microelect...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Liu DW,Gintant GA,Antzelevitch C

    更新日期:1993-03-01 00:00:00

  • Phorbol diester modulates alpha-adrenergic receptor-coupled calcium efflux and alpha-adrenergic receptor number in cultured vascular smooth muscle cells.

    abstract::The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate was used to probe the role of protein kinase-C in the modulation of alpha-adrenergic receptor-coupled calcium efflux in cultured vascular smooth muscle cells derived from rabbit aorta. Exposure of cells to 12-O-tetradecanoyl phorbol-13-acetate for 6 minutes cause...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Colucci WS,Gimbrone MA Jr,Alexander RW

    更新日期:1986-03-01 00:00:00

  • Ankyrin-G coordinates intercalated disc signaling platform to regulate cardiac excitability in vivo.

    abstract:RATIONALE:Nav1.5 (SCN5A) is the primary cardiac voltage-gated Nav channel. Nav1.5 is critical for cardiac excitability and conduction, and human SCN5A mutations cause sinus node dysfunction, atrial fibrillation, conductional abnormalities, and ventricular arrhythmias. Further, defects in Nav1.5 regulation are linked wi...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Makara MA,Curran J,Little SC,Musa H,Polina I,Smith SA,Wright PJ,Unudurthi SD,Snyder J,Bennett V,Hund TJ,Mohler PJ

    更新日期:2014-11-07 00:00:00

  • Critical roles for the Fas/Fas ligand system in postinfarction ventricular remodeling and heart failure.

    abstract::In myocardial infarction (MI), granulation tissue cells disappear via apoptosis to complete a final scarring with scanty cells. Blockade of this apoptosis was reported to improve post-MI ventricular remodeling and heart failure. However, the molecular biological mechanisms for the apoptosis are unknown. Fas and Fas li...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Li Y,Takemura G,Kosai K,Takahashi T,Okada H,Miyata S,Yuge K,Nagano S,Esaki M,Khai NC,Goto K,Mikami A,Maruyama R,Minatoguchi S,Fujiwara T,Fujiwara H

    更新日期:2004-09-17 00:00:00

  • Brain ouabain and central effects of dietary sodium in spontaneously hypertensive rats.

    abstract::High sodium intake (HNa) increases brain ouabainlike activity (OLA) in rats. In spontaneously hypertensive rats (SHR), HNa exaggerates development of hypertension and pressor and sympathoexcitatory responses to stress. To investigate whether dietary sodium-induced changes in brain OLA play a functional role, responses...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Huang BS,Leenen FH

    更新日期:1992-02-01 00:00:00

  • Analysis of Cardiac Myocyte Maturation Using CASAAV, a Platform for Rapid Dissection of Cardiac Myocyte Gene Function In Vivo.

    abstract:RATIONALE:Loss-of-function studies in cardiac myocytes (CMs) are currently limited by the need for appropriate conditional knockout alleles. The factors that regulate CM maturation are poorly understood. Previous studies on CM maturation have been confounded by heart dysfunction caused by whole organ gene inactivation....

    journal_title:Circulation research

    pub_type: 杂志文章,评审


    authors: Guo Y,VanDusen NJ,Zhang L,Gu W,Sethi I,Guatimosim S,Ma Q,Jardin BD,Ai Y,Zhang D,Chen B,Guo A,Yuan GC,Song LS,Pu WT

    更新日期:2017-06-09 00:00:00

  • miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling.

    abstract::The myocardium of the failing heart undergoes a number of structural alterations, most notably hypertrophy of cardiac myocytes and an increase in extracellular matrix proteins, often seen as primary fibrosis. Connective tissue growth factor (CTGF) is a key molecule in the process of fibrosis and therefore seems an att...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Duisters RF,Tijsen AJ,Schroen B,Leenders JJ,Lentink V,van der Made I,Herias V,van Leeuwen RE,Schellings MW,Barenbrug P,Maessen JG,Heymans S,Pinto YM,Creemers EE

    更新日期:2009-01-30 00:00:00

  • In vitro acetylcholine biosynthesis in normal and failing guinea pig hearts.

    abstract::Choline acetyltransferase activity, which is rate limiting in acetylcholine biosynthesis, was measured in the four heart chambers of guinea pigs subjected to (1) sham surgery, (2) constriction of the ascending aorta, (3) constriction of the descending thoracic aorta, and (4) constriction of the pulmonary artery. After...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Roskoski R Jr,Schmid PG,Mayer HE,Abboud FM

    更新日期:1975-04-01 00:00:00

  • Regulation of acetylcholinesterase in avian heart. Studies on ontogeny and the influence of vagotomy.

    abstract::This article examines the role of innervation in regulating expression of acetylcholinesterase (AchE), butyrylcholinesterase (BuchE), and the muscarinic acetylcholine receptor (mAchR) in avian heart. Two distinct approaches are taken. The first approach examines the relation between the onsets of parasympathetic and s...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Jo SA,Higgins DM,Berman HA

    更新日期:1992-04-01 00:00:00

  • Cardioprotection of preconditioning by metabolic inhibition in the rat ventricular myocyte. Involvement of kappa-opioid receptor.

    abstract::To determine whether opioid receptors (ORs) are involved in the delayed cardioprotection of ischemic preconditioning (IP), the effect of severe metabolic inhibition (MI) with a glucose-free buffer that contained sodium cyanide and 2-deoxy-D-glucose on the viability of isolated rat ventricular myocytes was first determ...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Wu S,Li HY,Wong TM

    更新日期:1999-06-25 00:00:00

  • Intramyocardial stem cell injection in patients with ischemic cardiomyopathy: functional recovery and reverse remodeling.

    abstract:RATIONALE:Transcatheter, intramyocardial injections of bone marrow-derived cell therapy produces reverse remodeling in large animal models of ischemic cardiomyopathy. OBJECTIVE:We used cardiac MRI (CMR) in patients with left ventricular (LV) dysfunction related to remote myocardial infarction (MI) to test the hypothes...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Williams AR,Trachtenberg B,Velazquez DL,McNiece I,Altman P,Rouy D,Mendizabal AM,Pattany PM,Lopera GA,Fishman J,Zambrano JP,Heldman AW,Hare JM

    更新日期:2011-04-01 00:00:00