Lactate per se improves the excitability of depolarised rat skeletal muscle by reducing the Cl- conductance

Frank Vincenzo de Paoli, Niels Ørtenblad, Thomas Holm Pedersen, Rasmus Jørgensen, Ole B Nielsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Studies on rats have shown that lactic acid can improve excitability and function of depolarized muscles. The effect has been related to the ensuing reduction in intracellular pH causing inhibition of muscle fibre Cl- channels. Since, however, several carboxylic acids with structural similarities to lactate can inhibit muscle Cl- channels it is possible that lactate per se can increase muscle excitability by exerting a direct effect on these channels. We therefore examined effects of lactate on the function of intact muscles and skinned fibres together with effects on pH and Cl- conductance. In muscles where extracellular compound action potentials (M-waves) and tetanic force response to excitation were reduced by 82±4 and 83±2 %, respectively, by depolarization with 11 mM extracellular K+, both M-waves and force exhibited an up to 4-fold increase when 20 mM lactate was added. This effect was present already at 5 mM and saturated at 15 mM lactate, and was associated with a 31 % reduction in GCl. The effects of lactate were completely blocked by Cl- channel inhibition or use of Cl- free solutions. Finally, both experiments where effects of lactate on intracellular pH in intact muscles were mimicked by increased CO2 tension, and experiments with skinned fibres showed that the effects of lactate could not be related to reduced intracellular pH. It is concluded that addition of lactate can inhibit ClC-1 Cl- channels and increase excitability and contractile function of depolarised rat muscles via mechanisms not related to a reduction in intracellular pH.
Original languageEnglish
JournalJournal of Physiology
Volume588
Issue number23
Pages (from-to)4785-4794
ISSN0022-3751
DOIs
Publication statusPublished - Oct 2010

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Lactic Acid
Skeletal Muscle
Muscles
Action Potentials

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de Paoli, Frank Vincenzo ; Ørtenblad, Niels ; Pedersen, Thomas Holm ; Jørgensen, Rasmus ; Nielsen, Ole B. / Lactate per se improves the excitability of depolarised rat skeletal muscle by reducing the Cl- conductance. In: Journal of Physiology. 2010 ; Vol. 588, No. 23. pp. 4785-4794.
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abstract = "Studies on rats have shown that lactic acid can improve excitability and function of depolarized muscles. The effect has been related to the ensuing reduction in intracellular pH causing inhibition of muscle fibre Cl- channels. Since, however, several carboxylic acids with structural similarities to lactate can inhibit muscle Cl- channels it is possible that lactate per se can increase muscle excitability by exerting a direct effect on these channels. We therefore examined effects of lactate on the function of intact muscles and skinned fibres together with effects on pH and Cl- conductance. In muscles where extracellular compound action potentials (M-waves) and tetanic force response to excitation were reduced by 82±4 and 83±2 {\%}, respectively, by depolarization with 11 mM extracellular K+, both M-waves and force exhibited an up to 4-fold increase when 20 mM lactate was added. This effect was present already at 5 mM and saturated at 15 mM lactate, and was associated with a 31 {\%} reduction in GCl. The effects of lactate were completely blocked by Cl- channel inhibition or use of Cl- free solutions. Finally, both experiments where effects of lactate on intracellular pH in intact muscles were mimicked by increased CO2 tension, and experiments with skinned fibres showed that the effects of lactate could not be related to reduced intracellular pH. It is concluded that addition of lactate can inhibit ClC-1 Cl- channels and increase excitability and contractile function of depolarised rat muscles via mechanisms not related to a reduction in intracellular pH.",
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Lactate per se improves the excitability of depolarised rat skeletal muscle by reducing the Cl- conductance. / de Paoli, Frank Vincenzo; Ørtenblad, Niels; Pedersen, Thomas Holm; Jørgensen, Rasmus; Nielsen, Ole B.

In: Journal of Physiology, Vol. 588, No. 23, 10.2010, p. 4785-4794.

Research output: Contribution to journalJournal articleResearchpeer-review

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T1 - Lactate per se improves the excitability of depolarised rat skeletal muscle by reducing the Cl- conductance

AU - de Paoli, Frank Vincenzo

AU - Ørtenblad, Niels

AU - Pedersen, Thomas Holm

AU - Jørgensen, Rasmus

AU - Nielsen, Ole B

PY - 2010/10

Y1 - 2010/10

N2 - Studies on rats have shown that lactic acid can improve excitability and function of depolarized muscles. The effect has been related to the ensuing reduction in intracellular pH causing inhibition of muscle fibre Cl- channels. Since, however, several carboxylic acids with structural similarities to lactate can inhibit muscle Cl- channels it is possible that lactate per se can increase muscle excitability by exerting a direct effect on these channels. We therefore examined effects of lactate on the function of intact muscles and skinned fibres together with effects on pH and Cl- conductance. In muscles where extracellular compound action potentials (M-waves) and tetanic force response to excitation were reduced by 82±4 and 83±2 %, respectively, by depolarization with 11 mM extracellular K+, both M-waves and force exhibited an up to 4-fold increase when 20 mM lactate was added. This effect was present already at 5 mM and saturated at 15 mM lactate, and was associated with a 31 % reduction in GCl. The effects of lactate were completely blocked by Cl- channel inhibition or use of Cl- free solutions. Finally, both experiments where effects of lactate on intracellular pH in intact muscles were mimicked by increased CO2 tension, and experiments with skinned fibres showed that the effects of lactate could not be related to reduced intracellular pH. It is concluded that addition of lactate can inhibit ClC-1 Cl- channels and increase excitability and contractile function of depolarised rat muscles via mechanisms not related to a reduction in intracellular pH.

AB - Studies on rats have shown that lactic acid can improve excitability and function of depolarized muscles. The effect has been related to the ensuing reduction in intracellular pH causing inhibition of muscle fibre Cl- channels. Since, however, several carboxylic acids with structural similarities to lactate can inhibit muscle Cl- channels it is possible that lactate per se can increase muscle excitability by exerting a direct effect on these channels. We therefore examined effects of lactate on the function of intact muscles and skinned fibres together with effects on pH and Cl- conductance. In muscles where extracellular compound action potentials (M-waves) and tetanic force response to excitation were reduced by 82±4 and 83±2 %, respectively, by depolarization with 11 mM extracellular K+, both M-waves and force exhibited an up to 4-fold increase when 20 mM lactate was added. This effect was present already at 5 mM and saturated at 15 mM lactate, and was associated with a 31 % reduction in GCl. The effects of lactate were completely blocked by Cl- channel inhibition or use of Cl- free solutions. Finally, both experiments where effects of lactate on intracellular pH in intact muscles were mimicked by increased CO2 tension, and experiments with skinned fibres showed that the effects of lactate could not be related to reduced intracellular pH. It is concluded that addition of lactate can inhibit ClC-1 Cl- channels and increase excitability and contractile function of depolarised rat muscles via mechanisms not related to a reduction in intracellular pH.

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