Effect of Mechanically Activated Calcium Channels on Passive Stiffness and Contraction Amplitude of Slow Muscle
摘要
The highly specialized mechanically activated (MA) Piezo1channel of the Piezo ion channel family has recently aroused increasedinterest among researchers because of its involvement in mammalian mechanotransduction.However, nothing has been known until now about the role of thischannel in the regulation of passive muscle stiffness and contraction.We hypothesized that both passive deformation of an isolated muscleand evoked single (twitch) and tetanic muscle contractions wouldlead to the activation of Piezo1 channels whose activity may increasepassive stiffness and muscle contraction amplitude. The study wasaimed to assess the possible contribution of Piezo1 channels tothe mechanical response of an isolated slow (soleus) muscle to passivedeformation and evoked twitch and tetanic contractions using Dooku1,a specific Piezo1 channel inhibitor, and gadolinium chloride (GdCl3),a nonspecific MA channel inhibitor. The experimental results showedthat the use of GdCl3 during passive stretchingled to a significant decrease in the indices of passive muscle stiffness.Interestingly, Dooku1-induced specific blockade of Piezo1 channelsdid not affect these indices. At the same time, when the isolatedmuscle was treated with Dooku1 solution, the maximum tension ofevoked twitch and tetanic contractions decreased by 21 and 25%,respectively. Also, incubation of muscles in GdCl3 solutionled to no significant changes in the indices of evoked contraction.Thus, we demonstrated that Piezo1 channels, which can be blockedby Gd3+, are stimulated by passive musclestretching and are involved in the regulation of passive musclestiffness. At the same time, Piezo1 channels are activated duringmuscle contraction and participate in its regulation. It can beassumed that the involvement of MA calcium channels in maintainingmuscle stiffness and the implementation of muscle contraction canbe achieved via the additional activation of myofibrils by calciumions whose concentration in muscle fibers increases due to activityof these channels.