Halothane reduces myofilament Ca2+ sensitivity during muscarinic receptor stimulation of airway smooth muscle

Academic Article

Abstract

  • This study used a β-escin-permeabilized canine tracheal smooth muscle preparation to test the hypothesis that the volatile anesthetic halothane decreases myofilament Ca2+ sensitivity by inhibiting the membrane receptor- linked second messenger systems that regulate myofilament Ca2+ sensitivity and not by inhibiting Ca2+-calmodulin activation of the contractile proteins. Acetylcholine (ACh) caused a GTP-dependent increase in force at constant submaximal cytosolic Ca2+ concentration. ACh, guanosine-5'-O-(3- thiotriphosphate), and the protein kinase C agonist 12, 13-phorbol dibutyrate each significantly decreased the concentration of free Ca2+ producing a half-maximal response from 0.77 ± 0.09 μM (Ca2+ alone) to 0.16 ± 0.01, 0.19 ± 0.02, and 0.37 ± 0.03 μM, respectively, demonstrating an increase in myofilament Ca2+ sensitivity. Halothane (0.92 ± 0.12 mM) had no effect on the free Ca2+ concentration-response curves generated by Ca2+ alone. However, in the presence of 3 μM ACh plus 10 μM GTP to maximally activate muscarinic receptors, halothane significantly increased the EC50 for free Ca2+ from 0.17 ± 0.01 μM to 0.38 ± 0.03 μM. These findings suggest that halothane decreases myofilament Ca2+ sensitivity in β-escin-permeabilized canine tracheal smooth muscle by inhibiting the membrane receptor-linked second messenger systems that regulate myofilament Ca2+ sensitivity.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Akao M; Hirasaki A; Jones KA; Wong GY; Bremerich DH; Warner DO
  • Volume

  • 271
  • Issue

  • 5 15-5