Reduced Sodium Pump α
 1
 , α
 3
 , and β
 1
 -Isoform Protein Levels and Na
 +
 ,K
 +
 -ATPase Activity but Unchanged Na
 +
 -Ca
 2+
 Exchanger Protein Levels in Human Heart Failure

Schwinger, Robert H. G.; Wang, Jiangnan; Frank, Konrad; Müller‐Ehmsen, Jochen; Brixius, Klara; McDonough, Alicia A.; Erdmann, Erland

doi:10.1161/01.cir.99.16.2105

Cited by 179 publications

(122 citation statements)

References 37 publications

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“…For example, NCX1 protein expression has been reported to decrease (71), increase (22,61,68), or remain unchanged (22,57) in HF. Although it is generally thought that SERCA2 mRNA levels decrease in CHF (3,11,29,55,61,68), no consensus exists in regard to protein levels, with some studies finding no change (29, 38 -40, 55, 56) and others a decrease (11,21,34,61,68) in expression.…”

Section: Discussionmentioning

confidence: 99%

Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats

Emter

McCune²,

Sparagna³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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. Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats. Am J Physiol Heart Circ Physiol 289: H2030 -H2038, 2005. First published July 1, 2005; doi:10.1152/ajpheart.00526.2005.-Data regarding the effectiveness of chronic exercise training in improving survival in patients with congestive heart failure (CHF) are inconclusive. Therefore, we conducted a study to determine the effect of exercise training on survival in a well-defined animal model of heart failure (HF), using the lean male spontaneously hypertensive HF (SHHF) rat. In this model, animals typically present with decompensated, dilated HF between ϳ18 and 23 mo of age. SHHF rats were assigned to sedentary or exercise-trained groups at 9 and 16 mo of age. Exercise training consisted of 6 mo of low-intensity treadmill running. Exercise training delayed the onset of overt HF and improved survival (P Ͻ 0.01), independent of any effects on the hypertensive status of the rats. Training delayed the myosin heavy chain (MyHC) isoform shift from ␣-to ␤-MyHC that was seen in sedentary animals that developed HF. Exercise was associated with a concurrent increase in cardiomyocyte length (Ϸ6%), width, and area and prevented the increase in the length-to-width ratio seen in sedentary animals in HF. The increases in proteinuria, plasma atrial natriuretic peptide, and serum leptin levels observed in rats with HF were suppressed by low-intensity exercise training. No significant alterations in sarco (endo)plasmic reticulum Ca 2ϩ ATPase, phospholamban, or Na ϩ / Ca 2ϩ exchanger protein expression were found in response to training. Our results indicate that 6 mo of low-intensity exercise training delays the onset of decompensated HF and improves survival in the male SHHF rat. Similarly, exercise intervention prevented or suppressed alterations in several key variables that normally occur with the development of overt CHF. These data support the idea that exercise may be a useful and inexpensive intervention in the treatment of HF. myosin heavy chain; proteinuria; cardiomyocyte morphology; atrial natriuretic peptide; leptin HEART DISEASE is a leading cause of death among men and women in Western industrialized societies. Cardiovascular disease (CVD) currently affects over 70 million Americans, 65 million of which are estimated to have high blood pressure and nearly 5 million are diagnosed with congestive heart failure (CHF) (2). With the diagnosis of CHF, life expectancy decreases dramatically and chances of survival decrease with 70 -80% of patients dying within 8 yr (2). Although chronic exercise training has clearly been shown to be beneficial in attenuating risk factors for CVD, including high blood pressure and cholesterol levels, insulin resistance, and obesity (9,14,53,58), the utility of exercise as a clinical intervention for patients with developing CHF is less clear. Currently, there is a lack of clarity regarding the efficacy of chronic exercise training as a treatment and in reducing mortali...

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Section: Discussionmentioning

confidence: 99%

Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats

Emter

McCune²,

Sparagna³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…This is somewhat surprising, considering that several biochemical studies revealed decreased expression and/or isoform shifts of the Na/K pump in failing or hypertrophied hearts. [13][14][15][16][17] However, most of these studies were performed in tissue homogenates and might reflect changes in nonmyocytes. Moreover, such measurements cannot differentiate between the internalized versus the sarcolemmal Na/K pumps 26 nor between functional and inactive pumps.…”

Section: [Na ؉ ] I Dependence Of the Na/k Pump Is Unchanged In Hf Myomentioning

confidence: 99%

“…12 Higher [Na ϩ ] i could be explained by lower Na/K pump activity, consistent with reports of decreased Na/K pump expression and isoform shifts in some HF models. [13][14][15][16][17] However, functional studies in HF ventricular myocytes are sparse and contradictory. 8,15 Enhanced Na ϩ influx could also raise [Na ϩ ] i , and this explains the higher [Na ϩ ] i in rat versus rabbit ventricular myocytes.…”

mentioning

confidence: 99%

Intracellular Na ⁺ Concentration Is Elevated in Heart Failure But Na/K Pump Function Is Unchanged

et al. 2002

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“…This property of the α3β2 isozyme may help in removing Na + ions efficiently from the cytoplasm in the intercalated disc, and as a result H + ions may turn out to be efficiently effluxed. The α3 isoform of the Na + ,K + -ATPase was reported to diminish in left ventricle of failing human myocardium [35]. Therefore, the diminished expression of the α3 isoform in the intercalated disc might account for the decline in the conduction velocity and the consequent arrhythmia in heart failure [36].…”

Section: Functions Of Na + K + -Atpase Isozymesmentioning

confidence: 99%

Subunit Composition and Role of Na+,K+-ATPases in Ventricular Myocytes

et al. 2006

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Na + ,K + -ATPases are composed of one α and one β subunit; four α and three β isoforms have been found to date. We elucidated which α and β subunits were present in the ventricular myocytes of rat and guinea-pig and what roles the Na + ,K + -ATPase isozymes play in cardiac contraction. The presence of the α1, α2, and α3 subunits and the β1 and β2 subunits in rat and guinea-pig hearts were confirmed at the protein or mRNA level. Immunocytochemistry showed a patchy presence of α1 in the transverse tubules and surface sarcolemma, whereas α2 was distributed continuously in the transverse tubules alone. The α3 isoform was expressed prominently in the guinea-pig intercalated disc and slightly in the rat. On the other hand, the β1 isoform was located in the transverse tubules and surface sarcolemma, whereas the β2 was mainly located in the intercalated disc. The immunocytochemistry and immunoprecipitation findings indicated that the α1 and α2 form heterodimers with β1 and the α3 with β2 in ventricular myocytes. The application of low concentrations of ouabain enhanced the amplitudes of twitch without a change in resting tension in rat and guinea-pig ventricular stripts, whereas that of high concentrations resulted in a decrease in twitch with an increase in the resting tension. We thus conclude that the α2β1 and α3β2 isozymes are selectively located in the transverse tubules and intercalated disc of the ventricular myocytes, respectively, and the α2β1 is involved in the regulation of the Ca 2+ contents in the SR.Key words: transverse tubules, intercalated disc, localization, Na + pump, subunits. Na + , K + -ATPases are heterodimers comprising α and β subunits [1]. There are four α and three β isoforms, and the expression of the α and β subunits have been reported to be developmentally regulated in a cell-specific manner [2]. Although the expression of α and β subunits in oocytes [3] or Sf-9 cells [1], an insect cell line, revealed every combination of α and β subunits was functional, Na + ,K + -ATPases in cells in situ are thought to exist as a specific combination of α and β subunits [4,5]. Furthermore, single cells have been shown to have multiple α subunits, which are distributed differently in the cell membrane [6]. We elucidated that the α1 subunit, which formed a heterodimer with the β3 subunit, was ubiquitously present in the cell membrane of adrenal chromaffin cells, whereas the α2 subunit, forming a heterodimer with the β2, was located in the cell membrane in the vicinity of Ca 2+ store sites [7]. Our functional and morphological analyses revealed that the α2 subunit was involved in the regulation of the Ca 2+ contents in intracellular Ca 2+ store sites and the α3 subunit was not expressed in chromaffin cells [7]. In astrocytes, the α2 subunit has also been shown to take part in regulating the Ca 2+ contents in Ca 2+ store sites, whereas the α1 subunit has only been assumed to play a house-keeping role [8]. On the other hand, a recent knock-in experiment revealed that the α1 subunit could regulate C...

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Reduced Sodium Pump α ₁ , α ₃ , and β ₁ -Isoform Protein Levels and Na ⁺ ,K ⁺ -ATPase Activity but Unchanged Na ⁺ -Ca ²⁺ Exchanger Protein Levels in Human Heart Failure

Abstract: The enhanced sensitivity of failing human myocardium toward cardiac glycosides may be, at least in part, attributed to a reduced protein expression and activity of the sarcolemmal Na+,K+-ATPase without a change in Na+-Ca2+ exchanger protein expression.

Cited by 179 publications

References 37 publications

Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats

Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats

Intracellular Na ⁺ Concentration Is Elevated in Heart Failure But Na/K Pump Function Is Unchanged

Subunit Composition and Role of Na+,K+-ATPases in Ventricular Myocytes

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Reduced Sodium Pump α 1 , α 3 , and β 1 -Isoform Protein Levels and Na + ,K + -ATPase Activity but Unchanged Na + -Ca 2+ Exchanger Protein Levels in Human Heart Failure

Abstract: The enhanced sensitivity of failing human myocardium toward cardiac glycosides may be, at least in part, attributed to a reduced protein expression and activity of the sarcolemmal Na+,K+-ATPase without a change in Na+-Ca2+ exchanger protein expression.

Cited by 179 publications

References 37 publications

Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats

Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats

Intracellular Na + Concentration Is Elevated in Heart Failure But Na/K Pump Function Is Unchanged

Subunit Composition and Role of Na+,K+-ATPases in Ventricular Myocytes

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Product

Resources

About

Reduced Sodium Pump α ₁ , α ₃ , and β ₁ -Isoform Protein Levels and Na ⁺ ,K ⁺ -ATPase Activity but Unchanged Na ⁺ -Ca ²⁺ Exchanger Protein Levels in Human Heart Failure

Intracellular Na ⁺ Concentration Is Elevated in Heart Failure But Na/K Pump Function Is Unchanged