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

Masaki Akao, Akihito Hirasaki, Keith A. Jones, Gilbert Y. Wong, Dorothee H. Bremerich, David Oman Warner

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume271
Issue number5 15-5
StatePublished - Nov 1996

Fingerprint

Myofibrils
Muscarinic Receptors
Halothane
Smooth Muscle
Escin
Acetylcholine
Second Messenger Systems
Guanosine Triphosphate
Canidae
Phorbol 12,13-Dibutyrate
Guanosine 5'-O-(3-Thiotriphosphate)
Contractile Proteins
Membranes
Calmodulin
Protein Kinase C
Anesthetics

Keywords

  • β-escin
  • 12,13-phorbol dibutyrate
  • acetylcholine
  • canine smooth muscle
  • fura 2
  • guanosine 5'- O-(3-thiotriphosphate)
  • halothane
  • lung
  • trachea

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Halothane reduces myofilament Ca2+ sensitivity during muscarinic receptor stimulation of airway smooth muscle. / Akao, Masaki; Hirasaki, Akihito; Jones, Keith A.; Wong, Gilbert Y.; Bremerich, Dorothee H.; Warner, David Oman.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 271, No. 5 15-5, 11.1996.

Research output: Contribution to journalArticle

Akao, Masaki ; Hirasaki, Akihito ; Jones, Keith A. ; Wong, Gilbert Y. ; Bremerich, Dorothee H. ; Warner, David Oman. / Halothane reduces myofilament Ca2+ sensitivity during muscarinic receptor stimulation of airway smooth muscle. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 1996 ; Vol. 271, No. 5 15-5.
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