Abstract 12826: Muscle Stretching Causes Membrane Excitation Without Activation of Stretch-Activated Channels in Intact Rat Trabeculae
Background: The occurrence of action potentials caused by cardiac muscle stretching has been termed as mechano-electric coupling (MEC). Stretch-activated channels (SACs) have been believed to play some important roles in MEC. We investigated what degree of muscle stretching can induce MEC-mediated membrane excitation and what roles SACs play in the excitation.
Methods: Trabeculae were obtained from rat hearts. Force was measured with a strain gauge, sarcomere length with a laser diffraction technique, and [Ca2+]i with fura-2 (24°C, 0.7 mmol/L [Ca2+]o). The sarcomere length (SL) was set at 2.0 μm at the resting condition. Trabeculae were stimulated electrically at 400 ms intervals for 7.5 s. Various degrees of muscle stretching were applied 500 ms after the last stimulus to determine the minimal SL (SLAP) at which an action potential or a twitch contraction was induced by stretching.
Results: The SLAP was 2.34 ± 0.02 μm (n = 8) when trabeculae were stretched rapidly from an SL of 2.0 μm. The SLAP was not changed significantly by increasing the stimulation interval from 400 to 2000 ms (n = 7), by increasing [Ca2+]o from 0.7 to 2 mM (n = 8), nor by adding 1 μM isoproterenol (n = 8). Surprisingly, it was not significantly changed in the presence of 5 μM GsMTx4 (n = 8), 10 mM Gd3+ (n = 9), 100 μM streptomycin (n = 8), nor 200 μM streptomycin (n = 11), revealing that SACs play no roles in the determination of SLAP. The SLAP was also not changed significantly in the presence of 1 μM ryanodine nor 10 μM carbenoxolone. The SLAP was increased from 2.35 ± 0.01 to 2.38 ± 0.01 μm (p<0.01, n = 7) by increasing extracellular K+ from 5 to 10 mM. In addition, it was increased from 2.34 ± 0.01 to 2.36 ± 0.01 μm (p<0.01, n = 7) when muscle stretching was applied after a shorter time, i.e., 200 ms after the last stimulus. Electrical stimulation at 300 ms stimulus intervals for 30 s induced arrhythmias in 6 out of 9 trabeculae when a stretch-induced contraction was applied 500 ms after the last stimulus (4 mM [Ca2+]o, 1 μM isoproterenol). In contrast, it induced arrhythmias in only 2 out of 9 trabeculae without the stretching.
Conclusions: These results suggest that muscle stretching causes membrane excitation, which potentially initiates arrhythmias, without activation of SACs nor Ca2+ release from the SR.
- © 2012 by American Heart Association, Inc.