How to make rapid eye movements "rapid": the role of growth factors for muscle contractile properties.

Different muscle functions require different muscle contraction properties. Saccade-generating extraocular muscles (EOMs) are the fastest muscles in the human body, significantly faster than limb skeletal muscles. Muscle contraction speed is subjected to plasticity, i.e., contraction speed can be adjusted to serve different demands, but little is known about the molecular mechanisms that control contraction speed. Therefore, we examined whether myogenic growth factors modulate contractile properties, including twitch contraction time (onset of force to peak force) and half relaxation time (peak force to half relaxation). We examined effects of three muscle-derived growth factors: insulin-like growth factor 1 (IGF1), cardiotrophin-1 (CT1), and glial cell line-derived neurotrophic factor (GDNF). In gain-of-function experiments, CT1 or GDNF injected into the orbit shortened contraction time, and IGF1 or CT1 shortened half relaxation time. In loss-of-function experiments with binding proteins or neutralizing antibodies, elimination of endogenous IGFs prolonged both contraction time and half relaxation time, while eliminating endogenous GDNF prolonged contraction time, with no effect on half relaxation time. Elimination of endogenous IGFs or CT1, but not GDNF, significantly reduced contractile force. Thus, IGF1, CT1, and GDNF have partially overlapping but not identical effects on muscle contractile properties. Expression of these three growth factors was measured in chicken and/or rat EOMs by real-time PCR. The "fast" EOMs express significantly more message encoding these growth factors and their receptors than skeletal muscles with slower contractile properties. Taken together, these findings indicate that EOM contractile kinetics is regulated by the amount of myogenic growth factors available to the muscle.