A troponin switch that regulates muscle contraction by stretch instead of calcium

The flight muscles of many insects have a form of regulation enabling them to contract at high frequencies. The muscles are activated by periodic stretches at low Ca²⁺ levels. The same muscles also give isometric contractions in response to higher Ca²⁺. We show that the two activities are controlled by different isoforms of TnC (F1 and F2) within single myofibrils. F1 binds one Ca²⁺ with high affinity in the C-terminal domain and F2 binds one Ca²⁺ in the C-terminal domain and one exchangeable Ca²⁺ in the N-terminal domain. We have characterised the isoforms and determined their effect on the development of stretch-activated and Ca²⁺-activated tension by replacing endogenous TnC in Lethocerus flight muscle fibres with recombinant isoforms. Fibres with F1 gave stretch-activated tension and minimal isometric tension; those with F2 gave Ca²⁺-dependent isometric tension and minimal stretch-activated tension. Regulation by a TnC responding to stretch rather than Ca²⁺ is unprecedented and has resulted in the ability of insect flight muscle to perform oscillatory work at low Ca²⁺ concentrations, a property to which a large number of flying insects owe their evolutionary success.