Ca2+ sensitivity of contractile activation during muscarinic stimulation of tracheal muscle.

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.