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 α-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.