Dexamethasone up-regulates skeletal muscle maximal Na⁺,K⁺ pump activity by muscle group specific mechanisms in humans

TY - JOUR

T1 - Dexamethasone up-regulates skeletal muscle maximal Na+,K+ pump activity by muscle group specific mechanisms in humans

AU - Nordsborg, Nikolai

AU - Goodmann, Craig

AU - McKenna, Michael J.

AU - Bangsbo, Jens

N1 - PUF 2005 5200 028

PY - 2005

Y1 - 2005

N2 - Dexamethasone, a widely clinically used glucocorticoid, increases human skeletal muscle Na+,K+ pump content, but the effects on maximal Na+,K+ pump activity and subunit specific mRNA are unknown. Ten healthy male subjects ingested dexamethasone for 5 days and the effects on Na+,K+ pump content, maximal activity and subunit specific mRNA level (a1, a2, ß1, ß2, ß3) in deltoid and vastus lateralis muscle were investigated. Before treatment, maximal Na+,K+ pump activity, as well as a1, a2, ß1 and ß2 mRNA levels were higher (P < 0.05) in vastus lateralis than in deltoid. Dexamethasone treatment increased Na+,K+ pump maximal activity in vastus lateralis and deltoid by 14 ± 7% (P < 0.05) and 18 ± 6% (P < 0.05) as well as Na+,K+ pump content by 18 ± 9% (P < 0.001) and 24 ± 8% (P < 0.01), respectively. Treatment with dexamethasone resulted in a higher a1, a2, ß1 and ß2 mRNA expression in the deltoid (P < 0.05), but no effects on Na+,K+ pump mRNA were detected in vastus lateralis. In conclusion, dexamethasone treatment increased maximal Na+,K+ pump activity in both vastus lateralis and deltoid muscles. The relative importance of transcription and translation in the glucocorticoid-induced regulation of Na+,K+ pump expression seems to be muscle specific and possibly dependent on the actual training condition of the muscle, such that a high Na+,K+ pump maximal activity and mRNA level prior to treatment prevents the transcriptional response to dexamethasone, but not the increase in Na+,K+ pump content and maximal activity.

AB - Dexamethasone, a widely clinically used glucocorticoid, increases human skeletal muscle Na+,K+ pump content, but the effects on maximal Na+,K+ pump activity and subunit specific mRNA are unknown. Ten healthy male subjects ingested dexamethasone for 5 days and the effects on Na+,K+ pump content, maximal activity and subunit specific mRNA level (a1, a2, ß1, ß2, ß3) in deltoid and vastus lateralis muscle were investigated. Before treatment, maximal Na+,K+ pump activity, as well as a1, a2, ß1 and ß2 mRNA levels were higher (P < 0.05) in vastus lateralis than in deltoid. Dexamethasone treatment increased Na+,K+ pump maximal activity in vastus lateralis and deltoid by 14 ± 7% (P < 0.05) and 18 ± 6% (P < 0.05) as well as Na+,K+ pump content by 18 ± 9% (P < 0.001) and 24 ± 8% (P < 0.01), respectively. Treatment with dexamethasone resulted in a higher a1, a2, ß1 and ß2 mRNA expression in the deltoid (P < 0.05), but no effects on Na+,K+ pump mRNA were detected in vastus lateralis. In conclusion, dexamethasone treatment increased maximal Na+,K+ pump activity in both vastus lateralis and deltoid muscles. The relative importance of transcription and translation in the glucocorticoid-induced regulation of Na+,K+ pump expression seems to be muscle specific and possibly dependent on the actual training condition of the muscle, such that a high Na+,K+ pump maximal activity and mRNA level prior to treatment prevents the transcriptional response to dexamethasone, but not the increase in Na+,K+ pump content and maximal activity.

U2 - 10.1113/jphysiol.2005.087031

DO - 10.1113/jphysiol.2005.087031

M3 - Journal article

C2 - 15975987

SN - 0022-3751

VL - 567

SP - 583

EP - 589

JO - Journal of Physiology

JF - Journal of Physiology

IS - 2

ER -