Farley_1978_J.Pharmacol.Exp.Ther_207_340

Acetylcholine (ACh)-induced contractions of dog tracheal smooth muscles were studied in order to determine the sources of Ca++ for these contractions become diminished with time at all drug doses and experiments with 45Ca indicate that this phenomenon is related to the efflux of Ca++ from the muscle. This efflux of Ca++ consists of two components, a loosely bound and a tightly bound Ca++ source, and is dependent upon the dose of drug. At low doses of ACh (less than 10(-6) M) loosely bound Ca++ plays a greater role and tightly bound Ca++ a lesser role than at higher drug doses. Verapamil, a blocker of depolarization-dependent Ca++ influx, inhibits ACh contractions at low drug doses but has no effect at higher doses. These results indicate that the sources of Ca++ for ACh contractions of the trachea are dependent upon the drug dose. At low doses of ACh (less than 10(-6) M ACh) depolarization-dependent Ca++ influx is involved in musch of the contraction. At the higher drug doses a tightly bound Ca++ source and a depolarization-independent, loosely bound Ca++ source account for the contractions.