The effect of mechano-activated channels on passive stiffness and contraction amplitude of slow muscle

Recently, highly specialized mechano-activated (MA) channels of the Piezo family have aroused increased interest among researchers in connection with their participation in the processes of mechanotransduction in mammals. However, until now nothing has been known about the role of these channels in the regulation of muscles’ passive stiffness and contraction. We assumed that both passive deformation of an isolated muscle and induced twitch and tetanic muscle contraction would lead to activation of Piezo1 channels, which increases passive stiffness and amplitude of muscle contraction. The purpose of the study: using Dooku1, a specific inhibitor of Piezo1 channels, and gadolinium chloride, a non-specific inhibitor of MA channels, to evaluate the possible contribution of Piezo1 channels to the mechanical response of an isolated slow muscle to passive deformation and induced twitch and tetanic contractions. The experimental results showed that the use of gadolinium led to a significant decrease in the parameters of passive muscle stiffness. Interestingly, the specific blocking of the Piezo1 MA channels using Dooku1 did not affect these parameters. At the same time, when the isolated muscle was treated with Dooku1 solution, the maximum tension of the induced twitch and tetanic contractions decreased by 21 and 25% respectively. Also, incubation of muscles in Gd³⁺ solution did not lead to significant changes in the parameters of induced contraction. Thus, we have shown that the MA channels, which can be blocked by Gd³⁺, are stimulated by passive muscle stretching and are involved in the regulation of muscle stiffness. At the same time, the Piezo1 MA channels are activated during muscle contraction and are involved in its regulation. It can be assumed that the participation of calcium channels in maintaining muscle stiffness and in the realization of muscle contraction can be carried out by additional activation of myofibrils with calcium ions, the concentration of which in muscle fiber increases as a result of the activity of these channels.