Calcium sensitization produced by G protein activation in airway smooth muscle.

We determined whether activation of G proteins can affect the force developed for a given intracellular Ca2+ concentration ([Ca2+]; i.e., the Ca2+ sensitivity) by mechanisms in addition to changes in regulatory myosin light chain (rMLC) phosphorylation. Responses in a-toxin-permeabilized canine tracheal smooth muscle were determined with Ca2+ alone or in the presence of ACh, endothelin-1 (ET-1), or aluminum fluoride (AlF4-; acute or 1-h exposure). Acute exposure to each compound increased Ca2+ sensitivity without changing the response to high [Ca2+] (maximal force). However, chronic exposure to AlF4-, but not to chronic ACh or ET-1, increased maximal force by increasing the force produced for a given rMLC phosphorylation. Studies employing thiophosphorylation of rMLC showed that the increase in force produced by chronic AlF4- exposure required Ca2+ during activation to be manifest. Unlike the acute response to receptor agonists, which is mediated solely by increases in rMLC phosphorylation, chronic direct activation of G proteins further increases Ca2+ sensitivity in airways by additional mechanisms that are independent of rMLC phosphorylation.