Sensitized airway smooth muscle plasticity and hyperreactivity: a reviewThis article is one of a selection of papers published in the Special Issue on Recent Advances in Asthma Research.
- 1 July 2007
- journal article
- review article
- Published by Canadian Science Publishing in Canadian Journal of Physiology and Pharmacology
- Vol. 85 (7), 679-685
- https://doi.org/10.1139/y07-061
Abstract
To help elucidate the mechanisms underlying asthmatic bronchospasm, the goal of our research has been to determine whether airway smooth muscle (ASM) hyperreactivity was the responsible factor. We reported that in a canine model of asthma, the shortening capacity (ΔLmax) and velocity (Vo) of in vitro sensitized muscle were significantly increased. This increase was of sufficient magnitude to account for 75% narrowing of the in vivo airway, but maximal isometric force was unchanged. This last feature has been reported by others. Under lightly loaded conditions, ASM completes 75% of its isotonic shortening within the first 2 s. Furthermore, 90% of the increased shortening of ragweed pollen-sensitized ASM (SASM), compared with control (CASM), is complete within the first 2 s. The study of shortening beyond this period will apparently not yield much useful information, and studies of isotonic shortening should be focused on this interval. Although both CASM and SASM showed plasticity and adaptation with respect to isometric force, neither muscle type showed a difference in the force developed in these phases. During isotonic shortening, no evidence of plasticity was seen, but the equilibrated SASM showed increased ΔLmaxand Voof shortening. Molecular mechanisms of changes in Vocould result from changes in the kinetics of the myosin heavy chain ATPase. Motility assay, however, showed no changes between CASM and SASM in the ability of the purified myosin molecule (SF1) to translocate a marker actin filament. On the other hand, we found that the state of activation of the ATPase by phosphorylation of smooth muscle myosin light chain (molecular mass 20 000 Da) was greater in the SASM. This would account for the increased Vo. Investigating the signalling pathway, we found that whereas [Ca2+]iincreased in both isometric and isotonic contraction, there was no significant difference between CASM and SASM. The content and activity of calmodulin were also not different between the 2 muscles. Nevertheless, we did find that content and total activity of smooth muscle myosin light chain kinase (smMLCK) and the abundance of its message were greater; this would explain the increased MLC20 phosphorylation. The binding affinity between Ca2+and calmodulin and between 4 Ca2+calmodulin and smMLCK remains to be studied. We conclude that SASM shows increased isotonic shortening capacity and velocity. It also shows increased content and total activity of smMLCK, which is consistent with the increased shortening. Plasticity produced by oscillation is not seen in the shortening muscle, although it is seen with respect to force development. It did not modulate the behaviour of the sensitized muscle.Keywords
This publication has 38 references indexed in Scilit:
- Isotonic relaxation of control and sensitized airway smooth muscleCanadian Journal of Physiology and Pharmacology, 2005
- Plasticity in airway smooth muscle: an updateCanadian Journal of Physiology and Pharmacology, 2005
- Mechanisms of mechanical strain memory in airway smooth muscleCanadian Journal of Physiology and Pharmacology, 2005
- Plasticity in canine airway smooth muscle.The Journal of general physiology, 1995
- Plasticity in smooth muscle, a hypothesisCanadian Journal of Physiology and Pharmacology, 1994
- The biophysics and biochemistry of smooth muscle contractionCanadian Journal of Physiology and Pharmacology, 1992
- Prolonged isobaric relaxation time in small mesenteric arteries of the spontaneously hypertensive ratCanadian Journal of Physiology and Pharmacology, 1987
- Tension–velocity relationships in hypertensive mesenteric resistance arteriesCanadian Journal of Physiology and Pharmacology, 1985
- Force–velocity relationships in hypertensive arterial smooth muscleCanadian Journal of Physiology and Pharmacology, 1985
- Isometric and isotonic contractions in airway smooth muscleCanadian Journal of Physiology and Pharmacology, 1977