Effects of verapamil on the response of the guinea-pig tracheal muscle to carbachol.

The effects of verapamil on the contraction of the guinea-pig tracheal smooth muscle induced by calcium (Ca2+) or barium (Ba2+) were investigated in three different conditions: (a) in excess K solution, (b) in the presence of carbachol, and (c) in excess K solution containing carbachol. In order to clarify the contractions, the effects of removal and readdition of the divalent cations were also investigated. In Ca2+-loaded tissues, application of carbachol in Ca-free medium produced a transient contraction, the magnitude of which decreased the longer the duration of exposure to Ca2+-free solution. In Ca2+-depleted, Ba2+-loaded tissues, application of carbachol in a Ba2+- and Ca2+-free medium produced a transient contraction the magnitude of which decreased the longer the duration of exposure to the Ba2+- and Ca2+-free solution. After exposure to Ca2+-free solution for 40 min, the sensitivity of the tissue to Ca2+ was greater in the presence of 30 microM carbachol (ED50 = 0.06 mM) than in the presence of 40 mM K+ (ED50 = 0.3 mM). The Ca2+-sensitivity in the presence of 30 microM carbachol plus K+ (40 mM) was not different from that in the presence of 30 microM carbachol alone. In Ca2+-free solution, the sensitivity of the tissue to Ba2+ in the presence of 40 mM K+ (ED50 = 1.4 mM) was not different from that observed in the presence of 30 microM carbachol (ED50 = 1.3 mM). 6 After exposure to Ca2+-free solution, verapamil produced a parallel rightward shift in the concentration-response curves to added Ca2+ and Ba2+ in the presence of either 40 mM K+, 30 microM carbachol or 40mM K+ plus 30 microM carbachol. 7 The pA2 values of verapamil against Ca2+ responses in the presence of 40 mM K+, 30 microM carbachol and 40 mM K+ plus 30 microM carbachol were 7.0, 6.5 and 6.5, respectively. The pA2 values of verapamil against Ba2+ responses under these conditions were 7.1, 7.0 and 7.1, respectively. 8 It is concluded that the sustained contraction produced by carbachol requires the influx of Ca2+ and that Ba2+ can substitute for Ca2+ in this process. Furthermore, the ionic channels which admit Ca2+ may be modified by carbachol to different degrees depending on the presence of Ca2+ or Ba2+. Such changes alter the affinity of the channel to verapamil.