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Regulation of the Na,K‐ATPase in skeletal muscle
Author(s) -
Kristensen Michael,
Juel Carsten
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a804
Subject(s) - bumetanide , chemistry , ouabain , cotransporter , medicine , endocrinology , potassium , skeletal muscle , atpase , sodium , biochemistry , enzyme , biology , organic chemistry
Muscle activity is associated with K + displacements, which may cause fatigue. Regulators of the K + homeostasis are the Na,K‐ATPase and the NKCC1 cotransporter. Our aim was to investigate the effect of increasing [K + ] e on K + uptake. The K + uptake was quantified from the 86Rb flux. The Rb uptake increased by 34% when increasing [K + ] e from 4 to 6 mM (P<0.05, n=6). At 4 mM K + there was a 29% reduction in Rb uptake (P<0.05, n=12) when incubating in Bumetanide, an inhibitor of NKCC, a 54% reduction with ouabain (P<0.05, n=7), and a 68% reduction with Bum + Oua (P<0.05, n=7). Discussion The Na,K‐pump is not expected to be very sensitive to external K + above 4 mM. Increasing [K + ] e to 6 mM increases the driving force for NKCC by approximately 20 %. NKCC only accounts for 15 % of the total K + uptake in resting muscles, thus, the increased activity of the NKCC can only explain a small fraction of the increase in Rb uptake. It is therefore possible that the increased Na + influx associated with the NKCC activity activates the Na,K‐ATPase. This is supported by inhibitor experiments. The inhibition of Rb uptake with bumetanide is larger than expected if the NKCC accounts for only 15% of the total K + uptake. Furthermore the reduction in Rb uptake when inhibiting both the NKCC and Na,K‐ATPase is less than expected. This indicate that a part of the reduced Rb uptake when inhibiting the NKCC is due to a reduction of the Na + activation of the Na,K‐ATPase. Alternatively: There seem to be a co‐localisation between the Na,K‐ATPase and caveolin‐3 indicating that the Na,K‐ATPase is present in caveolae. If caveolae are K + “deficient” an increase in [K + ] e to 6 mM could activate the Na,K‐ATPase and increased Rb uptake.