Stretch-activated ion channels contribute to membrane depolarization after eccentric contractions

We tested the hypothesis that eccentric contractionsactivate mechanosensitive or stretch-activated ion channels (SAC) in skeletal muscles, producing increased cation conductance.Resting membrane potentials and contractile function were measured in rat tibialis anterior muscles after single or multiple exposures to aseries of eccentric contractions. Each exposure produced a significantand prolonged (>24 h) membrane depolarization in exercised musclefibers. The magnitude and duration of the depolarization were relatedto the number of contractions. Membrane depolarization was dueprimarily to an increase in Na⁺ influx, because theestimated Na⁺-to-K⁺ permeability ratio wasincreased in exercised muscles and resting membrane potentials could bepartially repolarized by substituting an impermeant cation forextracellular Na⁺ concentration. Neither theNa⁺/H⁺ antiport inhibitor amiloride nor thefast Na⁺ channel blocker TTX had a significant effect onthe depolarization. In contrast, addition of either of two nonselectiveSAC inhibitors, streptomycin or Gd³⁺, produced significantmembrane repolarization. The results suggest that muscle fibersexperience prolonged depolarization after eccentric contractions due,principally, to the activation of Na⁺-selective SAC.