Sodium pump isoform expression in heart failure: implication for treatment

2002 ◽  
Vol 97 (7) ◽  
pp. 1-1 ◽  
Author(s):  
Jochen M�ller-Ehmsen ◽  
Robert A. Farley ◽  
Robert H. G. Schwinger ◽  
Alicia A. McDonough
2003 ◽  
Vol 94 (6) ◽  
pp. 2225-2236 ◽  
Author(s):  
Bryan Helwig ◽  
Katherine M. Schreurs ◽  
Joslyn Hansen ◽  
K. Sue Hageman ◽  
Michael G. Zbreski ◽  
...  

The mechanisms responsible for the decrements in exercise performance in chronic heart failure (CHF) remain poorly understood, but it has been suggested that sarcolemmal alterations could contribute to the early onset of muscular fatigue. Previously, our laboratory demonstrated that the maximal number of ouabain binding sites (Bmax) is reduced in the skeletal muscle of rats with CHF (Musch TI, Wolfram S, Hageman KS, and Pickar JG. J Appl Physiol 92: 2326–2334, 2002). These reductions may coincide with changes in the Na+-K+-ATPase isoform (α and β) expression. In the present study, we tested the hypothesis that reductions in Bmax would coincide with alterations in the α- and β-subunit expression of the sarcolemmal Na+-K+-ATPase of rats with CHF. Moreover, we tested the hypothesis that exercise training would increase Bmax along with producing significant changes in α- and β-subunit expression. Rats underwent a sham operation (sham; n = 10) or a surgically induced myocardial infarction followed by random assignment to either a control (MI; n = 16) or exercise training group (MI-T; n = 16). The MI-T rats performed exercise training (ET) for 6–8 wk. Hemodynamic indexes demonstrated that MI and MI-T rats suffered from severe left ventricular dysfunction and congestive CHF. Maximal oxygen uptake (V˙o 2 max) and endurance capacity (run time to fatigue) were reduced in MI rats compared with sham. Bmax in the soleus and plantaris muscles and the expression of the α2-isoform of the Na+-K+-ATPase in the red portion of the gastrocnemius (gastrocnemiusred) muscle were reduced in MI rats. After ET, V˙o 2 max and run time to fatigue were increased in the MI-T group of rats. This coincided with increases in soleus and plantaris Bmax and the expression of the α2-isoform in the gastrocnemiusred muscle. In addition, the expression of the β2-isoform of the gastrocnemiusred muscle was increased in the MI-T rats compared with their sedentary counterparts. This study demonstrates that CHF-induced alterations in skeletal muscle Na+-K+-ATPase, including Bmax and isoform expression, can be partially reversed by ET.


2002 ◽  
Vol 92 (1) ◽  
pp. 18-24 ◽  
Author(s):  
Espen E. Spangenburg ◽  
Simon J. Lees ◽  
Jeff S. Otis ◽  
Timothy I. Musch ◽  
Robert J. Talmadge ◽  
...  

It is thought that changes in sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) of skeletal muscle contribute to alterations in skeletal muscle function during congestive heart failure (CHF). It is well established that exercise training can improve muscle function. However, it is unclear whether similar adaptations will result from exercise training in a CHF patient. Therefore, the purpose of this study was to determine whether skeletal muscle during moderate CHF adapts to increased activity, utilizing the functional overload (FO) model. Significant increases in plantaris mass of the CHF-FO and sham-FO groups compared with the CHF and control (sham) groups were observed. Ca2+ uptake rates were significantly elevated in the CHF group compared with all other groups. No differences were detected in Ca2+ uptake rates between the CHF-FO, sham, and sham-FO groups. Increases in Ca2+ uptake rates in moderate-CHF rats were not due to changes in SERCA isoform proportions; however, FO may have attenuated the CHF-induced increases through alterations in SERCA isoform expression. Therefore, changes in skeletal muscle Ca2+handling during moderate CHF may be due to alterations in regulatory mechanisms, which exercise may override, by possibly altering SERCA isoform expression.


2009 ◽  
Vol 33 (7) ◽  
pp. 1103-1106 ◽  
Author(s):  
Humera Hamid ◽  
YongLin Gao ◽  
Zhenmin Lei ◽  
M. Tyler Hougland ◽  
Rif S. El-Mallakh

Circulation ◽  
1999 ◽  
Vol 99 (16) ◽  
pp. 2105-2112 ◽  
Author(s):  
Robert H. G. Schwinger ◽  
Jiangnan Wang ◽  
Konrad Frank ◽  
Jochen Müller-Ehmsen ◽  
Klara Brixius ◽  
...  

1998 ◽  
Vol 275 (3) ◽  
pp. R926-R932 ◽  
Author(s):  
Tsung-Han Lee ◽  
Jong-Chang Tsai ◽  
Mei-Jane Fang ◽  
Ming-Jiun Yu ◽  
Pung-Pung Hwang

Three isoform-specific antibodies, 6F against the α1-isoform of the avian sodium pump, HERED against the rat α2-isoform, and Ax2 against the rat α3-isoform, were used to detect the expression of Na+-K+-ATPase α-subunits in gills of a teleost, the tilapia ( Oreochromis mossambicus). Tilapia gill tissue showed positive reactions to antibodies specific for α1- and α3-isoforms. The results of immunoblots were converted to numerical values (relative intensities) by image analysis for comparisons. Relative amounts of α1-like isoform alone and consequently the ratio of α1-like to α3-like isoforms were higher in gills of seawater-adapted tilapia than in those of freshwater-adapted ones, indicating that the two isoforms respond differently to environmental salinities. In the subsequent immunocytochemical experiments, gill mitochondria-rich cells were demonstrated to immunoreact with antibodies specific for α1- and α3-isoforms. α1-like and α3-like isoforms of gill Na+-K+-ATPase are suggested to be involved in the ion- and osmoregulation mechanisms in tilapia. Moreover, differential expressions of two isoforms may be associated with different functions, secretion and uptake of ions and acid-base regulation, in gills of seawater- and freshwater-adapted tilapia.


1997 ◽  
Vol 273 (2) ◽  
pp. H707-H717 ◽  
Author(s):  
P. Ping ◽  
T. Anzai ◽  
M. Gao ◽  
H. K. Hammond

We examined alterations in left ventricular (LV) G protein receptor kinase (GRK) and adenylyl cyclase (AC) isoform expression during the development of pacing-induced congestive heart failure (CHF). AC isoform and GRK expression were assessed 4 (mild CHF) and 28 (severe CHF) days after initiation of pacing. LV beta-adrenergic receptor (beta-AR) number and G protein content were unchanged by mild CHF. LV AC isoform mRNA content was unaltered by mild CHF, but there were increases in total GRK activity (P < 0.01), total GRK5 protein content (P < 0.04), and GRK5 mRNA (P = 0.003); total GRK2 protein content and GRK2 mRNA were unchanged. Mild CHF was associated with decreased beta-AR coupling (P < 0.01) and reduced beta-AR stimulation of AC (P < 0.05). Severe CHF was associated with LV beta-AR downregulation (P = 0.0001) and uncoupling (P < 0.001) and marked generalized reduction of AC activity (mean P = 0.01). LV ACVI isoform mRNA content was reduced (P = 0.002), but ACII and ACV isoform mRNA contents were unaffected. Persistent elevations in LV total GRK activity (P < 0.01), total GRK5 protein content (P < 0.001), and GRK5 mRNA (P = 0.01) were found; in contrast, total GRK2 protein content was unchanged and GRK2 mRNA was reduced (P = 0.02). These studies indicate that increased GRK activity is an early charge in heart failure that predates alterations in AC isoform expression. Impaired hormonal stimulation of AC, associated with beta-AR uncoupling, may result from increased GRK5 expression. AC downregulation is isoform specific and accompanies severe but not mild CHF.


2002 ◽  
Vol 20 (6) ◽  
pp. 1189-1194 ◽  
Author(s):  
Alexander I. Fridman ◽  
Sergei A. Matveev ◽  
Natalia I. Agalakova ◽  
Olga V. Fedorova ◽  
Edward G. Lakatta ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document