Muscle stretching induces twitch contractions without activation of stretch-activated channels in intact rat trabeculae
| Autor: | Haruka Sato, Chiyohiko Shindoh, Masahito Miura, K Kumasaka, Wakako Satoh |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | European Heart Journal. 42 |
| ISSN: | 1522-9645 0195-668X |
| DOI: | 10.1093/eurheartj/ehab724.3205 |
| Popis: | Introduction Mechano-electric coupling (MEC) means that muscle stretching can induce action potentials. Stretch-activated channels (SACs) have been believed to play important roles in their induction. Purpose To investigate what degree of muscle stretching can induce MEC-mediated action potentials and what roles SACs play in their induction. Methods Trabeculae were obtained from right ventricles of rat hearts. Force was measured with a strain gauge, sarcomere length (SL) with a laser diffraction technique, and [Ca2+]i with fura-2 (24°C). The 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 at 500 ms after the last stimulus of the electrical train to determine the minimal SL (SL-AP) at which an action potential or a twitch contraction was induced by the stretching (0.7 mM [Ca2+]o). Results The SL-AP was 2.34±0.02 μm (n=8) when trabeculae were stretched rapidly from a SL of 2.0 μm (400-ms stimulation intervals, 0.7 mM [Ca2+]o). The SL-AP was not changed by increasing the stimulation intervals from 400 to 2000 ms (n=7), by increasing [Ca2+]o from 0.7 to 2 mM (n=8), and by adding 1 μM isoproterenol (n=8), suggesting that Ca2+ loading within the myocardium has no effect on the SL-AP. Surprisingly, the SL-AP was not changed by adding 5 μM GsMTx4 (n=8), 10 mM Gd3+ (n=9), 100 μM (n=8) and 200 μM streptomycin (n=11), revealing that SACs play no roles in the determination of SL-AP. The SL-AP was not changed by adding 1 μM ryanodine (n=5) and 30 μM cyclopiazonic acid and was not changed by adding 3 μM diphenyleneiodonium chloride (n=8) and 10 μM colchicine, suggesting that Ca2+ leak from the SR and activation of NADPH oxidase has no effect on the SL-AP. In contrast, elevation of temperature from 23 to 36°C decreased the SL-AP from 2.35±0.01 to 2.34±0.02 μm (p Conclusions These results suggest that muscle stretching causes membrane excitation, which potentially induces arrhythmias and that activation of SACs, Ca2+ release from the SR, and activation of NADPH oxidase by muscle stretching are not involved in the excitation. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid for Scientific Research (C) from Japan Society for the Promotion of Science. |
| Databáze: | OpenAIRE |
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