Effects of Verapamil on the Contractions of Guinea-pig Tracheal Muscle Induced by Ca, Sr and Ba

A comparison was made of contractions produced by calcium (Ca), strontium (Sr) or barium (Ba) in guinea-pig tracheal smooth muscle after the preparation had been relaxed in Ca-free medium. Most of the experiments were carried out in the presence of indomethacin (5 microM) to inhibit endogenous prostaglandin synthesis. In 40 mM K+ solution, the Ca, Sr and Ba concentrations which produced 50% of maximum tension responses were 0.07 mM, 1 mM and 2 mM, respectively. Maximum tension of a similar size was produced by either 2.4 mM Ca, 9.6 mM Sr or 9.6 mM Ba. The Ca-induced contraction in 5.9 mM K solution, which is probably due to the presence of endogenous prostaglandins, was not significantly affected by verapamil. When the external K concentration was increased to 40 mM, the Ca-induced contraction became susceptible to inhibition by verapamil. Similarly, contractions induced by Sr and Ba in excess K solution were strongly suppressed by verapamil. In the presence of prostaglandin (PG) F2 alpha (1.4 microM) or carbachol (5 microM), Ca, Sr and Ba produced contractions in both the 5.9 mM K and 40 mM K solutions. Contractions produced by PGF2 alpha or carbachol in the presence of Ca were little affected by 10 microM verapamil, whereas those in the presence of Sr or Ba were strongly suppressed by verapamil in both the 5.9 and 40 mM K solutions. 4 A strong suppressant effect of verapamil on the K-induced contraction, but a weak effect on the drug-induced contraction, in the presence of Ca can be explained by assuming that verapamil blocks voltage-operated Ca channels, but not receptor-operated Ca channels. However, this theory cannot account for the effect of verapamil on drug-induced contractions in the presence of Sr or Ba. It may be that susceptibility to verapamil is determined by the relative affinity of'the divalent cations and verapamil for the Ca channels, both for voltage- and receptor-operated channels.