Resting membrane potential and intracellular [Na ⁺ ] at rest, during fatigue and during recovery in rat soleus muscle fibres in situ.

Publisher: Cambridge Univ. Press Country of Publication: England NLM ID: 0266262 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-7793 (Electronic) Linking ISSN: 00223751 NLM ISO Abbreviation: J Physiol Subsets: MEDLINE

Publication: Oxford : Blackwell : Cambridge Univ. Press
Original Publication: London, Cambridge Univ. Press.

Muscle Fatigue*/physiology ; Membrane Potentials*/physiology ; Muscle Fibers, Skeletal*/physiology ; Muscle Fibers, Skeletal*/metabolism ; Sodium*/metabolism; Animals ; Male ; Rats ; Muscle, Skeletal/physiology ; Rats, Wistar ; Sodium-Potassium-Exchanging ATPase/metabolism ; Rest/physiology ; Muscle Contraction/physiology ; Electric Stimulation

Large trans-sarcolemmal ionic shifts occur with fatiguing exercise or stimulation of isolated muscles. However, it is unknown how resting membrane potential (E M ) and intracellular sodium concentration ([Na ⁺ ] i ) change with repeated contractions in living mammals. We investigated (i) whether [Na ⁺ ] i (peak, kinetics) can reveal changes of Na ⁺ -K ⁺ pump activity during brief or fatiguing stimulation and (ii) how resting E M and [Na ⁺ ] i change during fatigue and recovery of rat soleus muscle in situ. Muscles of anaesthetised rats were stimulated with brief (10 s) or repeated tetani (60 Hz for 200 ms, every 2 s, for 30 s or 300 s) with isometric force measured. Double-barrelled ion-sensitive microelectrodes were used to quantify resting E M and [Na ⁺ ] i . Post-stimulation data were fitted using polynomials and back-extrapolated to time zero recovery. Mean pre-stimulation resting E M (layer 2-7 fibres) was -71 mV (surface fibres were more depolarised), and [Na ⁺ ] i was 14 mM. With deeper fibres, 10 s stimulation (2-150 Hz) increased [Na ⁺ ] i to 38-46 mM whilst simultaneously causing hyperpolarisations (7.3 mV for 2-90 Hz). Fatiguing stimulation for 30 s or 300 s led to end-stimulation resting E M of -61 to -53 mV, which recovered rapidly (T 1/2 , 8-22 s). Mean end-stimulation [Na ⁺ ] i increased to 86-101 mM with both fatigue protocols and the [Na ⁺ ] i recovery time-course (T 1/2 , 21-35 s) showed no difference between protocols. These combined findings suggest that brief stimulation hyperpolarises the resting E M , likely via maximum Na ⁺ -induced stimulation of the Na ⁺ -K ⁺ pump. Repeated tetani caused massive depolarisation and elevations of [Na ⁺ ] i that together lower force, although they likely interact with other factors to cause fatigue. [Na ⁺ ] i recovery kinetics provided no evidence of impaired Na ⁺ -K ⁺ pump activity with fatigue. KEY POINTS: It is uncertain how resting membrane potential, intracellular sodium concentration ([Na ⁺ ] i ), and sodium-potassium (Na ⁺ -K ⁺ ) pump activity change during repeated muscle contractions in living mammals. For rat soleus muscle fibres in situ, brief tetanic stimulation for 10 s led to raised [Na ⁺ ] i , anticipated to evoke maximal Na ⁺ -induced stimulation of the Na ⁺ -K ⁺ pump causing an immediate hyperpolarisation of the sarcolemma. More prolonged stimulation with repeated tetanic contractions causes massive elevations of [Na ⁺ ] i , which together with large depolarisations (via K ⁺ disturbances) likely reduce force production. These effects occurred without impairment of Na ⁺ -K ⁺ pump function. Together these findings suggest that rapid activation of the Na ⁺ -K ⁺ pump occurs with brief stimulation to maintain excitability, whereas more prolonged stimulation causes rundown of the trans-sarcolemmal K ⁺ gradient (hence depolarisation) and Na ⁺ gradient, which in combination can impair contraction to contribute to fatigue in living mammals.
(© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

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Natural Sciences and Engineering Research Council of Canada (NSERC); Anders Jahres Fond til Vitenskapens Fremme (Anders Jahre's Foundation for the Promotion of Science); Wynette Griffiths Research Trust

Keywords: Na+‐K+‐ATPase; depolarisation; hyperpolarisation; maximal sodium transport; sodium–potassium pump

9NEZ333N27 (Sodium)
EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)

Date Created: 20240615 Date Completed: 20240715 Latest Revision: 20240715

20240716

10.1113/JP285870

38877870