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

Abstract

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