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

Abstract

We tested the hypothesis that eccentric contractions activate 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 a series of eccentric contractions. Each exposure produced a significant and prolonged (>24 h) membrane depolarization in exercised muscle fibers. The magnitude and duration of the depolarization were related 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 could be partially repolarized by substituting an impermeant cation for extracellular Na(+) concentration. Neither the Na(+)/H(+) antiport inhibitor amiloride nor the fast Na(+) channel blocker TTX had a significant effect on the depolarization. In contrast, addition of either of two nonselective SAC inhibitors, streptomycin or Gd(3+), produced significant membrane repolarization. The results suggest that muscle fibers experience prolonged depolarization after eccentric contractions due, principally, to the activation of Na(+)-selective SAC.

Histological Skeletal Muscle Damage and Surface EMG Relationships Following Eccentric Contractions

“…For example, in the early phase following EC, focal degenerative and inflammatory responses in damaged muscle fiber are accompanied by alteration of membrane depolarization [35] and fiber edema [16]. Previous studies [26,36] also demonstrated the presence of necrotic muscle fibers with macrophage invasion at 1 to 3 days after injury and muscle fiber regeneration with myoblasts and myotubes at 4 days after [37].…”

Intracellular calcium accumulation following eccentric contractions in rat skeletal muscle in vivo: role of stretch-activated channels

“…It has been determined that streptomycin and Gd 3ϩ function as SAC blockers in working skeletal muscle from healthy rat (31,32,42,53) or mdx mouse (52,55,56). However, the specificity of these agents is often brought into question.…”

Effects of Eccentric Exercise on Cycling Efficiency

“…It has been reported that the loss of muscle strength after eccentric exercise is caused by both peripheral (Ingalls et al, 1998;McBride et al, 2000;Michaut et al, 2002;Warren et al, 1993;Yeung et al, 2002) and central (Gibala et al, 1995;Michaut et al, 2002;Millet et al, 2003) mechanisms. Among the peripheral mechanisms, animal experiments have provided compelling evidence for a failure in neuromuscular transmission and sarcolemmal excitability, caused by excitationcontraction uncoupling (Ingalls et al, 1998;Warren et al, 1993;Yeung et al, 2002) and persistent activation of mechanosensitive or stretch-activated ion channels (McBride et al, 2000).…”

“…Among the peripheral mechanisms, animal experiments have provided compelling evidence for a failure in neuromuscular transmission and sarcolemmal excitability, caused by excitationcontraction uncoupling (Ingalls et al, 1998;Warren et al, 1993;Yeung et al, 2002) and persistent activation of mechanosensitive or stretch-activated ion channels (McBride et al, 2000).…”

“…It may be of particular interest to determine if the degree of muscle damage is attenuated when the eccentric exercise is combined with concentric exercise. It could also be of interest to determine if this combination of exercise prevents the persistent activation of mechanosensitive or stretch-activated ion channels described by McBride et al (2000). Finally, whether the combination of eccentric and concentric exercise prevents the impairment in the process of neural activation observed when eccentric exercise is performed alone needs to be established.…”