Premium
Relationship between membrane Cl − conductance and contractile endurance in isolated rat muscles
Author(s) -
de Paoli Frank Vincenzo,
BrochLips Martin,
Pedersen Thomas Holm,
Nielsen Ole Bækgaard
Publication year - 2013
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2012.243246
Subject(s) - conductance , biophysics , chemistry , membrane , anatomy , physics , biology , biochemistry , condensed matter physics
Key points• Excitable cells commonly regulate their ability to generate and propagate action potentials through modulating the properties of the membrane ion channels. Recently it was shown that muscle activity is associated with rapid, protein kinase C (PKC)‐dependent ClC‐1 Cl − channel inhibition. • Here the functional significance of this ClC‐1 inhibition for contractile endurance was determined in isolated slow‐ and fast‐twitch rat muscles. • Experiments showed that PKC inhibition led to reduced contractile endurance, an effect of PKC that disappeared when extracellular Cl − was removed or ClC‐1 channels were inhibited. • Experiments where resting Cl − conductance ( G Cl ) was manipulated by reduction of solution Cl − or inhibition of ClC‐1 Cl − channels suggest a biphasic dependency of contractile endurance on G Cl with an optimum close to the G Cl observed in active muscles. • The biphasic relation between G Cl and endurance seems to reflect that lowered G Cl on one side increases muscle excitability but on the other side reduces the ability of the muscle fibres to maintain K + homeostasis and membrane potential during contractions. • This study suggested that PKC‐dependent ClC‐1 Cl − channel regulation is important for the maintenance of contractile endurance in working muscle.Abstract Resting skeletal muscle fibres have a large membrane Cl − conductance ( G Cl ) that dampens their excitability. Recently, however, muscle activity was shown to induce PKC‐mediated reduction in G Cl in rat muscles of 40–90%. To examine the physiological significance of this PKC‐mediated G Cl reduction for the function of muscles, this study explored effects of G Cl reductions on contractile endurance in isolated rat muscles. Contractile endurance was assessed from the ability of muscle to maintain force during prolonged stimulation under conditions when G Cl was manipulated by: (i) inhibition of PKC, (ii) reduction of solution Cl − or (iii) inhibition of ClC‐1 Cl − channels using 9‐anthracene‐carboxylic acid (9‐AC). Experiments showed that contractile endurance was optimally preserved by reductions in G Cl similar to what occurs in active muscle. Contrastingly, further G Cl reductions compromised the endurance. The experiments thus show a biphasic relationship between G Cl and contractile endurance in which partial G Cl reduction improves endurance while further G Cl reduction compromises endurance. Intracellular recordings of trains of action potentials suggest that this biphasic dependency of contractile endurance on G Cl reflects that lowering G Cl enhances muscle excitability but low G Cl also increases the depolarisation of muscle fibres during excitation and reduces their ability to re‐accumulate K + lost during excitation. If G Cl becomes very low, the latter actions dominate causing reduced endurance. It is concluded that the PKC‐mediated ClC‐1 channel inhibition in active muscle reduces G Cl to a level that optimises contractile endurance during intense exercise.