Nitric oxide and Na,K-ATPase activity in rat skeletal muscle

TY - JOUR

T1 - Nitric oxide and Na,K-ATPase activity in rat skeletal muscle

AU - Juel, Carsten

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Aim: It has been suggested that nitric oxide (NO) stimulates the Na,K-ATPase in cardiac myocytes. Therefore, the aims of this study were to investigate whether NO increases Na,K-ATPase activity in skeletal muscle and, if that is the case, to identify the underlying mechanism. Method: The study used isolated rat muscle, muscle homogenates and purified membranes as model systems. Na,K-ATPase activity was quantified from phosphate release due to ATP hydrolysis. Results: Exposure to the NO donor spermine NONOate (10 μm) increased the maximal Na,K-ATPase activity by 27% in isolated glycolytic muscles, but had no effect in oxidative muscles. Spermine NONOate increased the maximal Na,K-ATPase activity by 58% (P <0.05) in homogenates from glycolytic muscle, but had no effect in oxidative muscle. The stimulatory effect of NONOate was not related to one specific Na,K-ATPase α-isoform. Incubation with cGMP (1 mm) increased the maximal Na,K-ATPase activity in homogenates from glycolytic muscle by 16% (P <0.05), but had no effect on homogenates from oxidative muscle. cGMP had no effect on phospholemman phosphorylation at serine 68. Spermine NONOate had no effect in muscle membranes in which the ATPase activity was depressed by oxidized glutathione. Conclusion: NO and cGMP stimulate the Na,K-ATPase in glycolytic skeletal muscle. Direct S-nitrosylation and interference with S-glutathionylation seem to be excluded. In addition, phosphorylation of phospholemman at serine 68 is not involved. Most likely, the NO/cGMP/protein kinase G signalling pathway is involved.

AB - Aim: It has been suggested that nitric oxide (NO) stimulates the Na,K-ATPase in cardiac myocytes. Therefore, the aims of this study were to investigate whether NO increases Na,K-ATPase activity in skeletal muscle and, if that is the case, to identify the underlying mechanism. Method: The study used isolated rat muscle, muscle homogenates and purified membranes as model systems. Na,K-ATPase activity was quantified from phosphate release due to ATP hydrolysis. Results: Exposure to the NO donor spermine NONOate (10 μm) increased the maximal Na,K-ATPase activity by 27% in isolated glycolytic muscles, but had no effect in oxidative muscles. Spermine NONOate increased the maximal Na,K-ATPase activity by 58% (P <0.05) in homogenates from glycolytic muscle, but had no effect in oxidative muscle. The stimulatory effect of NONOate was not related to one specific Na,K-ATPase α-isoform. Incubation with cGMP (1 mm) increased the maximal Na,K-ATPase activity in homogenates from glycolytic muscle by 16% (P <0.05), but had no effect on homogenates from oxidative muscle. cGMP had no effect on phospholemman phosphorylation at serine 68. Spermine NONOate had no effect in muscle membranes in which the ATPase activity was depressed by oxidized glutathione. Conclusion: NO and cGMP stimulate the Na,K-ATPase in glycolytic skeletal muscle. Direct S-nitrosylation and interference with S-glutathionylation seem to be excluded. In addition, phosphorylation of phospholemman at serine 68 is not involved. Most likely, the NO/cGMP/protein kinase G signalling pathway is involved.

KW - Exercise

KW - Muscle physiology

KW - Na,K-pump

U2 - 10.1111/apha.12617

DO - 10.1111/apha.12617

M3 - Journal article

C2 - 26472244

SN - 1748-1708

VL - 216

SP - 447

EP - 453

JO - Acta Physiologica

JF - Acta Physiologica

IS - 4

ER -