Stretch-activated ion channels contribute to membrane depolarization aftereccentric contractions

We tested the hypothesis that eccentric contractions activate mechanosensit ive or stretch-activated ion channels (SAC) in skeletal muscles, producing increased cation conductance. Resting membrane potentials and contractile f unction were measured in rat tibialis anterior muscles after single or mult iple exposures to a series of eccentric contractions. Each exposure produce d a significant and prolonged (>24 h) membrane depolarization in exercised muscle fibers. The magnitude and duration of the depolarization were relate d to the number of contractions. Membrane depolarization was due primarily to an increase in Na+ influx, because the estimated Na+-to-K+ permeability ratio was increased in exercised muscles and resting membrane potentials co uld be partially repolarized by substituting an impermeant cation for extra cellular Na+ concentration, Neither the Na+/H+ antiport inhibitor amiloride nor the fast Na+ channel blocker TTX had a significant effect on the depol arization. In contrast, addition of either of two nonselective SAC inhibito rs, streptomycin or Gd3+, produced significant membrane repolarization. The results suggest that muscle fibers experience prolonged depolarization aft er eccentric contractions due, principally, to the activation of Na+-select ive SAG.