The importance of decreased Cl ‐ channel activity in preventing K + ‐induced force depression at the onset of muscle activity (1102.17)

Interstitial [K + ] reaches 10‐12 mM even in non‐fatiguing muscle activity. At low stimulation frequencies (1‐90 Hz) and 37°C, peak force is potentiated at these [K + ], and force depression in mouse EDL muscle occurs only when [K + ] exceeds 13 mM. Partial decreases in Cl ‐ channel activity allows for force recovery at elevated [K + ] while complete block of Cl ‐ channel activity worsens the K + ‐induced force depression. The objective of this study was to determine the optimal level of Cl ‐ channel activity or conductance (GCl). Increasing K + from 4.7 (control) to 13 mM reduced peak force by 75%. Subsequent exposure to 9‐AC, a ClC‐1 Cl ‐ channel blocker, allowed for an increase in force being 25%, 26% and 43% at 6.5, 10 and 20 µM 9‐AC, respectively. At 40 and 100 µM 9‐AC, the force increases were smaller, being 15% and 9%, respectively; i.e., an optimum effect was observed at 20 µM 9‐AC. Interestingly, at 20 µM 9‐AC, the GCl is expected to be about 30% of the normal GCl at rest. More importantly, there is evidence for a 70% decrease in GCl at the onset of a muscle activity. We therefore suggest that this decrease in GCl at the onset of exercise play a critical role in preventing K + , which rapidly reaches 10‐12 mM, to depress membrane excitability and force generation and in fact maintain the K + ‐induced force thereby improving muscle performance. Grant Funding Source : CIHR