Re-acceleration of the down-regulated contraction kinetics in the rat tracheal smooth muscle

Abstract

The contraction kinetics of smooth muscle show a down-regulation after the transient rise found during sustained contraction. We tried to find out therefore if the contraction kinetics of rat tracheal smooth muscle can be re-accelerated during sustained activation. A 2 s length vibration (100 Hz sinusoidal; amplitude=6% of the muscle length) produces an immediate fall in the force developed by the activated muscle. A biexponential function was fitted to the force recovery. The reciprocal of the time constant,t ₂, describing the slow component of force recovery, reflects the kinetics of contraction. The contraction kinetics reach their highest levels (t ₂=4.9±0.1 s,n=166) about 30 s after the onset of electrical field stimulation. Three experimental groups were activated by either 10 μM serotonin (5-HT), 100 μM acetylcholine (ACh), or by 2 μM ACh for 50 min. Approximately 10 vibrations were applied to each preparation after an 8 min activation in order to observe stabilized down-regulated contraction kinetics.t ₂ values were calculated from the force recovery after vibration and averaged 11.2±0.2 s (n=141), 11.5±0.2 s (n=137), and 11.1±0.3 s (n=84), respectively. After 50 min of continuous chemical activation, the preparation was stimulated additionally by the neurogenic release of acetylcholine. Thet ₂ of post-vibration force recovery, as measured after 30 s of neural activation, showed no change in the specimens basically activated by 100 μM ACh (11.0±0.4 s,n=51). A decline int ₂, indicating accelerated kinetics, was observed in the groups which had been stimulated by 10 μM 5-HT (5.9±0.2 s,n=51) and 2 μM ACh (5.6±0.2 s,n=47). The re-accelerating effect of the second stimulus could be reproduced recurrently. The down-regulated contraction kinetics can be re-accelerated either by activating another receptor type in addition to the one already maximally stimulated or by increasing the stimulus mediated by one of the receptor types from half maximal to maximal strength. However, this is only possible if the additional activation is strong enough, as indicated by an increase in active force. It could be demonstrated that the slowing of the cross-bridge cycling rate is the result of a regulatory process and not the result of substrate deficiencies or refractoriness in the regulatory of contractile proteins.