Potassium-induced potentiation of subtetanic force in rat skeletal muscles: influences of β₂-activation, lactic acid, and temperature

Abstract

Purpose: Moderate elevations of [K+]o occur during exercise and have been shown to potentiate force during contractions elicited with subtetanic frequencies. Here, we investigated whether lactic acid (reduced chloride conductance), β2-adrenoceptor activation, and increased temperature would influence the potentiating effect of potassium in slow- and fast-twitch muscle. Methods: Isometric contractions were elicited by electrical stimulation at various frequencies in isolated rat soleus and extensor digitorum longus (EDL) muscles incubated at normal (4 mM) or elevated K+, in combination with either salbutamol (5 μM), lactic acid (18.1 mM), 9-AC (25 μM) or increased temperature (30 to 35°C). Results: Elevating [K+] from 4 mM to 7 mM (soleus) and 10 mM (EDL) potentiated isometric twitch and subtetanic force while slightly reducing tetanic. In EDL, salbutamol further augmented twitch force (+27±3 %, P<0.001) and subtetanic force (+22±4 %, P<0.001). In contrast, salbutamol reduced subtetanic force (-28±6 %, P<0.001) in soleus muscles. Lactic acid and 9-AC had no significant effects on isometric force of muscles already exposed to moderate elevations of [K+]o. The potentiating effect of elevated [K+]o was still well maintained at 35°C. Conclusion: Addition of salbutamol exerts a further force-potentiating effect in fast-twitch but not in slow-twitch muscles already potentiated by moderately elevated [K+]o, whilst neither lactic acid, 9-AC nor increased temperature exerts any further augmentation. However, the potentiating effect of elevated [K+]o was still maintained in the presence of these, thus emphasizing the positive influence of moderately elevated [K+]o for contractile performance during exercise.

Piperine enhances contractile force in slow‐ and fast‐twitch muscle

“…Force potentiation by moderately increased extracellular K + is another important physiological mechanism to acutely modulate muscle function, and this type of potentiation is present in both fast‐ and slow‐twitch fibres. K + ‐induced potentiation also shares the property with piperine potentiation that only force elicited at low frequencies is potentiated, while tetanic force is unaltered or slightly depressed (Olesen et al., 2021; Overgaard et al., 2022; Pedersen et al., 2019). However, K + ‐induced potentiation is thought to be linked to a membrane potential depolarization leading to altered Ca 2+ handling and increased Ca 2+ spikes during activation (Pedersen et al., 2019; Quiñonez et al., 2010), while we did not observe changes in Ca 2+ handling with piperine incubation.…”

“…To check the reversibility of any piperine effects, washout experiments with piperine were performed using an isometric force transducer system, also previously described (Olesen et al., 2021). Isometric force measurements were made on EDL ( n = 4) and soleus muscles ( n = 4) every 15 min at 2, 50 and 150 Hz (EDL) or 2, 15 and 60 Hz (soleus) while muscles were exposed to KR buffer solution with or without piperine (50 μM).…”

Exercise and fatigue: integrating the role of K+, Na+ and Cl− in the regulation of sarcolemmal excitability of skeletal muscle

“…There is a reasonably well established association between glycolytically-derived ATP and NKA activity and strong evidence to support the concept that glycolysis and NKA are functionally coupled. This seems to be an evolutionary conserved coupling and has been observed in several tissue types, including mammalian erythrocytes (Kennedy et al 1986 ; Mercer and Dunham 1981 ; Schrier 1966 ), axons (Caldwell et al 1960 ); brain synaptosomes (Erecińska and Dagani 1990 ), kidney cells (Lynch and Balaban 1987 ), smooth muscle (Campbell and Paul 1992 ), cardiac myocytes (Hasin and Barry 1984 ; MacLeod 1989 ; Philipson and Nishimoto 1983 ) and skeletal muscles (Clausen 1965 ; James et al 1999a ; Jensen et al 2020 ; Okamoto et al 2001 ). This is supported by the observation that a number of tissue types generate both pyruvate and lactate under primarily aerobic conditions in a process linking glycolytic ATP supply to NKA activity (Brooks 1986 ; Dhar-Chowdhury et al 2007 ).…”

“…Such a tight coupling between the glycogenolytic rate and NKA activity is demonstrated by the observation that [Na + ] i decreases if glycogen breakdown is stimulated with epinephrine at rest, whilst ouabain attenuates glycogen utilization (James et al 1999b ). Also, experiments using ouabain and measurements of myoplasmic high-energy phosphates, in resting rat EDL muscles, demonstrated that NKA activity is only suppressed when glycolysis is inhibited and not affected by inhibition of oxidative phosphorylation; this suggests that normal glycolysis is the predominant source of the fuel for NKA (Okamoto et al 2001 ). In support, an early study by Clausen was one of the first to demonstrate a link between muscle glycogenolysis and NKA activity, showing that glycogen utilization in resting muscle was decreased when muscle NKA activity was blocked by ouabain (Clausen 1965 ).…”