Potassium Regulation of the NaK-ATPase Pump Currents in Mammalian Skeletal Muscle Fibers

Abstract

effect of tetrapropylammonium (TPA) and Beryllium Fluoride (BeFx) on inward proton current (IH) transport by NKA expressed in Xenopus oocytes. TPA (a shared site blocker) had a dual effect on IH; between pH 7.6-6.0 TPA partially inhibited IH, and at pH 5.0 (where an inhibitory effect on the steady state IH is present), TPA partially activated IH. When the phosphate analogue BeFx was injected into oocytes, stabilizing an externally open conformation of the ion binding sites, K þ still inhibited inward current at pH 7.6. At pH 5.0 K þ activated IH resembling the effect of TPA on fully functional NKA. These results illustrate the complex interaction between the occupancy of shared sites and proton permeation. Blocking access at the shared sites with TPA activated IH by relieving the inhibition normally observed at high [H þ ]. Partial inhibition by TPA at pH 5.0 may reflect incomplete block of H þ access or a reduced rate of the conformational changes needed for H þ translocation. After BeFx inhibition NKA was still capable of interacting with K þ. The mixed occupancy of K þ and H þ at low pH activated the leak, likely relieving the H þ inhibition due to K þ occlusion.

Effects of lowered [Na+]o and membrane depolarization on the Ca2+ transients of fast skeletal muscle fibers. Implications for muscle fatigue

“…While this has the beneficial effect of increasing K + reuptake from the TTS [32], it also have the detrimental effect of reducing the space constant of the TTS, further compromising radial propagation. Increased K + o upregulated NaK-pump activity [34, 35]. This may help limiting changes in transmembrane K + and Na + gradients during activity [36], thus limiting fatigue development.…”

“…The actual endowment of ion transport systems in the TTS is still a matter of debate (see for example [41][42][43]), but most probably, it is different from that of the surface membrane in terms of channel density, stoichiometry, and isoforms present. For example, different isoforms of the NaK-pump are present at each membrane compartment of murine muscle fibers, making them physiologically different [34,44]. Although only one Na + channel isoform prevails in adult fibers (NaV1.1), Na + channels at the TTS and surface membranes may work differently due to differences in lipid environment.…”