AJP - Cell Physiology, Vol 263, Issue 6 C1258-C1265, Copyright © 1992 by American Physiological Society
Ca2+ sensitivity of contractile activation during muscarinic stimulation of tracheal muscle
S. J. Gunst, W. T. Gerthoffer and M. H. al-Hassani
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46202.
The muscarinic agonists acetylcholine (ACh) and McN-A-343 act on a
homogenous population of M3 receptors in canine tracheal smooth muscle;
however, ACh is more effective at releasing stored Ca2+ and at stimulating
inositol phosphate production. The effects of ACh and McN-A-343 on
intracellular Ca2+ concentration ([Ca2+]i), myosin light chain (MLC)
phosphorylation, active stress, and isotonic shortening velocity were
compared to determine whether differences in their potency at stimulating
second messenger pathways affected their ability to modulate the Ca2+
sensitivity of contractile filament activation. There were no differences
in [Ca2+]i or isometric stress during the steady-state phase of submaximal
contractions induced by ACh and McN-A-343. ACh produced slightly higher
levels of MLC phosphorylation than McN-A-343; these levels were associated
with much higher rates of isotonic shortening. This could indicate either
an extremely high sensitivity of the shortening velocity to differences in
MLC phosphorylation or that mechanisms other than MLC phosphorylation
contribute to the regulation of shortening velocity. Results show that
receptor-coupled pathways can modulate the relationship between [Ca2+]i and
isotonic shortening velocity independently of the relationship between
[Ca2+]i and isometric stress.
