Protein kinase C {alpha} activity is important for contraction-induced FXYD1 phosphorylation in skeletal muscle

TY - JOUR

T1 - Protein kinase C {alpha} activity is important for contraction-induced FXYD1 phosphorylation in skeletal muscle

AU - Thomassen, Martin

AU - Rose, Adam John

AU - Jensen, Thomas Elbenhardt

AU - Maarbjerg, Stine Just

AU - Bune, Laurids Touborg

AU - Leitges, Michael

AU - Richter, Erik

AU - Bangsbo, Jens

AU - Nordsborg, Nikolai Baastrup

N1 - CURIS 2011 5200 118

PY - 2011/12

Y1 - 2011/12

N2 - Exercise-induced phosphorylation of FXYD1 is a potential important regulator of Na +-K +-pump activity. It was investigated whether skeletal muscle contractions induce phosphorylation of FXYD1 and whether protein kinase Cα (PKCα) activity is a prerequisite for this possible mechanism. In part 1, human muscle biopsies were obtained at rest, after 30 s of high-intensity exercise (166 ± 31% of V ̇ O2max) and after a subsequent 20 min of moderate-intensity exercise (79 ± 8% ofV ̇ O 2max). In general, FXYD1 phosphorylation was increased compared with rest both after 30 s (P < 0.05) and 20 min (P < 0.001), and more so after 20 min compared with 30 s (P < 0.05). Specifically, FXYD1 ser63, ser68, and combined ser68 and thr69 phosphorylation were 26-45% higher (P < 0.05) after 20 min of exercise than at rest. In part 2, FXYD1 phosphorylation was investigated in electrically stimulated soleus and EDL muscles from PKCα knockout (KO) and wild-type (WT) mice. Contractile activity caused FXYD1 ser68 phosphorylation to be increased (P < 0.001) in WT soleus muscles but to be reduced (P < 0.001) in WT extensor digitorum longus. In contrast, contractile activity did not affect FXYD1 ser68 phosphorylation in the KO mice. In conclusion, exercise induces FXYD1 phosphorylation at multiple sites in human skeletal muscle. In mouse muscles, contraction-induced changes in FXYD1 ser68 phosphorylation are fiber-type specific and dependent on PKCα activity.

AB - Exercise-induced phosphorylation of FXYD1 is a potential important regulator of Na +-K +-pump activity. It was investigated whether skeletal muscle contractions induce phosphorylation of FXYD1 and whether protein kinase Cα (PKCα) activity is a prerequisite for this possible mechanism. In part 1, human muscle biopsies were obtained at rest, after 30 s of high-intensity exercise (166 ± 31% of V ̇ O2max) and after a subsequent 20 min of moderate-intensity exercise (79 ± 8% ofV ̇ O 2max). In general, FXYD1 phosphorylation was increased compared with rest both after 30 s (P < 0.05) and 20 min (P < 0.001), and more so after 20 min compared with 30 s (P < 0.05). Specifically, FXYD1 ser63, ser68, and combined ser68 and thr69 phosphorylation were 26-45% higher (P < 0.05) after 20 min of exercise than at rest. In part 2, FXYD1 phosphorylation was investigated in electrically stimulated soleus and EDL muscles from PKCα knockout (KO) and wild-type (WT) mice. Contractile activity caused FXYD1 ser68 phosphorylation to be increased (P < 0.001) in WT soleus muscles but to be reduced (P < 0.001) in WT extensor digitorum longus. In contrast, contractile activity did not affect FXYD1 ser68 phosphorylation in the KO mice. In conclusion, exercise induces FXYD1 phosphorylation at multiple sites in human skeletal muscle. In mouse muscles, contraction-induced changes in FXYD1 ser68 phosphorylation are fiber-type specific and dependent on PKCα activity.

U2 - 10.1152/ajpregu.00066.2011

DO - 10.1152/ajpregu.00066.2011

M3 - Journal article

C2 - 21957166

SN - 0363-6119

VL - 301

SP - R1808-R1814

JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology

JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology

IS - 6

ER -