Calcium sensitization produced by G protein activation in airway smooth muscle

We determined whether activation of G proteins can affect the force develop ed for a given intracellular Ca2+ concentration ([Ca2+]; i.e., the Ca2+ sen sitivity) by mechanisms in addition to changes in regulatory myosin light c hain (rMLC) phosphorylation. Responses in a-toxin-permeabilized canine trac heal smooth muscle were determined with Ca2+ alone or in the presence of AC h, endothelin-1 (ET-1), or aluminum fluoride (AlF4-; acute or 1-h exposure) . Acute exposure to each compound increased Ca2+ sensitivity without changi ng the response to high [Ca2+] (maximal force). However, chronic exposure t o AlF4-, but not to chronic ACh or ET-1, increased maximal force by increas ing the force produced for a given rMLC phosphorylation. Studies employing thiophosphorylation of rMLC showed that the increase in force produced by c hronic AlF4- exposure required Ca2+ during activation to be manifest. Unlik e the acute response to receptor agonists, which is mediated solely by incr eases in rMLC phosphorylation, chronic direct activation of G proteins furt her increases Ca2+ sensitivity in airways by additional mechanisms that are independent of rMLC phosphorylation.