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

Am J Physiol Regul Integr Comp Physiol. 2008 Apr;294(4):R1329-37. doi: 10.1152/ajpregu.00815.2007. Epub 2008 Jan 16.


Although the accumulation of intracellular calcium ions ([Ca2+]i) is associated with muscle damage, little is known regarding the temporal profile of muscle [Ca2+]i under in vivo conditions, and, specifically, the effects of different contraction types [e.g., isometric (ISO); eccentric (ECC)] on [Ca2+]i remain to be determined. The following hypotheses were tested. 1) For 90 min at rest, an in vivo vs. in vitro preparation would better maintain initial [Ca2+]i. 2) Compared with ISO, ECC contractions (50 contractions, 10 sets, 5-min interval) would lead to a greater increase of [Ca2+]i. 3) Elevated [Ca2+]i during ECC would be reduced or prevented by the stretch-activated ion channel blockers streptomycin and gadolinium (Gd3+). Spinotrapezius muscles of Wistar rats were exteriorized (in vivo) or excised (in vitro). [Ca2+]i was evaluated by loading the muscle with fura 2-AM using fluorescence imaging. [Ca2+]i rose progressively beyond 40 min at rest under in vitro but not in vivo conditions during the 90-min protocol. In vivo [Ca2+]i increased more rapidly during ECC (first set) than ISO (fifth set) (P < 0.05 vs. precontraction values). The peak level of [Ca2+]i was increased by 21.5% (ISO) and 42.8% (ECC) after 10 sets (both P < 0.01). Streptomycin and Gd3+ abolished the majority of [Ca2+]i increase during ECC (69 and 86% reduction, respectively; P < 0.01 from peak [Ca2+]i of ECC). In conclusion, in vivo quantitative analyses demonstrated that ECC contractions elevate [Ca2+]i significantly more than ISO contractions and that stretch-activated channels may play a permissive role in this response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Gadolinium / pharmacology
  • Ion Channel Gating* / drug effects
  • Ion Channels / antagonists & inhibitors
  • Ion Channels / metabolism*
  • Isometric Contraction
  • Kinetics
  • Male
  • Membrane Transport Modulators / pharmacology
  • Microscopy, Fluorescence
  • Microscopy, Video
  • Muscle Contraction* / drug effects
  • Muscle Spindles / metabolism*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Rats
  • Rats, Wistar
  • Research Design
  • Streptomycin / pharmacology
  • Up-Regulation


  • Ion Channels
  • Membrane Transport Modulators
  • Gadolinium
  • Calcium
  • Streptomycin