Roles of stretch-activated channels and NADPH oxidase 2 in the induction of twitch contraction by muscle stretching in rat ventricular muscle

Abstract

Mechano-electric feedback means that muscle stretching causes depolarization of membrane potential. We investigated whether muscle stretching induces action potential and twitch contraction with a threshold of sarcomere length (SL) and what roles stretch-activated channels (SACs) and stretch-activated NADPH oxidase (X-ROS signaling) play in the induction. Trabeculae were obtained from the right ventricles of rat hearts. Force, SL, and [Ca2+]i were measured. Various degrees of stretching from the SL of 2.0μm were applied 0.5s after the last stimulus of the electrical train with 0.4-s intervals for 7.5s. The SLtwitch was defined as the minimal SL at which twitch contraction was induced by the stretching. Muscle stretching induced twitch contraction with a threshold of SL at 0.4-s stimulus intervals ([Ca2+]o = 0.7mmol/L). The SLtwitch was not changed by increasing the stimulus intervals and [Ca2+]o and by adding 1μmol/L isoproterenol. The SLtwitch was not changed by adding 10μmol/L Gd3+, 100μmol/L or 200μmol/L streptomycin, and 5μmol/L GsMTx4. The SLtwitch was not changed by adding 1μmol/L ryanodine and 3μmol/L diphenyleneiodonium chloride. In contrast, the SLtwitch was increased by elevating extracellular K+ from 5 to 10mmol/L and by adding the stretching during the refractory period of membrane potential. The addition of the stretching-induced twitch contraction more frequently induced arrhythmias. These results suggest that muscle stretching can induce twitch contraction with a threshold of SL and concern the occurrence of arrhythmias and that SACs and X-ROS signaling play no roles in the induction.