Skeletal Muscle Na,K-ATPase as a Target for Circulating Ouabain.

Violetta V Kravtsova,Igor I Krivoi,Elena V Bouzinova,Vladimir V Matchkov

doi:10.3390/ijms21082875

Violetta V Kravtsova, Igor I Krivoi + Show 2 more

Open Access

https://doi.org/10.3390/ijms21082875

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Abstract

While the role of circulating ouabain-like compounds in the cardiovascular and central nervous systems, kidney and other tissues in health and disease is well documented, little is known about its effects in skeletal muscle. In this study, rats were intraperitoneally injected with ouabain (0.1–10 µg/kg for 4 days) alone or with subsequent injections of lipopolysaccharide (1 mg/kg). Some rats were also subjected to disuse for 6 h by hindlimb suspension. In the diaphragm muscle, chronic ouabain (1 µg/kg) hyperpolarized resting potential of extrajunctional membrane due to specific increase in electrogenic transport activity of the α2 Na,K-ATPase isozyme and without changes in α1 and α2 Na,K-ATPase protein content. Ouabain (10–20 nM), acutely applied to isolated intact diaphragm muscle from not injected rats, hyperpolarized the membrane to a similar extent. Chronic ouabain administration prevented lipopolysaccharide-induced (diaphragm muscle) or disuse-induced (soleus muscle) depolarization of the extrajunctional membrane. No stimulation of the α1 Na,K-ATPase activity in human red blood cells, purified lamb kidney and Torpedo membrane preparations by low ouabain concentrations was observed. Our results suggest that skeletal muscle electrogenesis is subjected to regulation by circulating ouabain via the α2 Na,K-ATPase isozyme that could be important for adaptation of this tissue to functional impairment.

Highlights

Na,K-ATPase is a vital transport protein that is ubiquitously expressed in the plasma membrane of all animal cells
Our study suggests that the extrajunctional pool of α2 Na,K-ATPase is activated by circulating ouabain
Twenty-four hours after the last ouabain (1 μg/kg) injection, rats were subjected to HS, widely used as an animal model of disuse that leads to progressive atrophy of postural skeletal muscles

Summary

Introduction

Na,K-ATPase is a vital transport protein that is ubiquitously expressed in the plasma membrane of all animal cells. The Na,K-ATPase is responsible for establishing and maintaining high K+ and low Na+ concentrations in the cytoplasm. This ion translocation activity underlies the resting membrane potential (RMP) as well as membrane excitability and provides the driving force for secondary ion transport [1]. Four isoforms of the α subunit and three isoforms of the β subunit are expressed in a cell- and tissue-specific manner providing a wide molecular diversity of the Na,K-ATPase. The α1 and α2 isoforms are co-expressed in skeletal, cardiac and smooth muscles as well as in glial cells, while the α1 and α3 isoforms are characteristic for neuronal tissues [5,6,7,8,9]

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