Effects of halothane on sarcoplasmic reticulum calcium release channels in porcine airway smooth muscle cells

Christina M. Pabelick, Yedatore S. Prakash, Mathur S. Kannan, David O. Warner, Gary C. Sieck

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Background: Volatile anesthetics relax airway smooth muscle (ASM) by altering intracellular Ca2+ concentration ([Ca2+]1). The authors hypothesized that relaxation is produced by decreasing sarcoplasmic reticulum Ca2+ content via increased Ca2+ "leak" through both inositol trisphosphate (IP3) and ryanodine receptor channels. Methods: Enzymatically dissociated porcine ASM cells were exposed to acetylcholine in the presence or absence of 2 minimum alveolar concentration (MAC) halothane, and IP3 levels were measured using radioimmunoreceptor assay. Other cells were loaded with the Ca2+ indicator fluo-3 and imaged using real-time confocal microscopy. Results: Halothane increased IP3 concentrations in the presence and absence of acetylcholine. Inhibition of phospholipase C blunted the IP3 response to halothane. Exposure to 2 MAC halothane induced a transient [Ca2+]1 response, suggesting depletion of sarcoplasmic reticulum Ca2+. Exposure to 20 μM Xestospongin D, a cell-permeant IP3 receptor antagonist, resulted in a 45 ± 13% decrease in the [Ca2+)1 response to halothane compared with halothane exposure alone. In permeabilized cells, Xestospongin D or 0.5 mg/ml heparin decreased the [Ca2+]1 response to halothane by 65 ± 13% and 68 ± 22%, respectively, compared with halothane alone. In both intact and permeabilized cells, 20 μM ryanodine blunted the [Ca2+]1 response to halothane by 32 ± 13% and 39 ± 21%, respectively, compared with halothane alone. Simultaneous exposure to Xestospongin D and ryanodine completely inhibited the [Ca2+]1 response to halothane. Conclusions: The authors conclude that halothane reduces sarcoplasmic reticulum Ca2+ content in ASM cells via increased Ca2+ leak through both IP3 receptor and ryanodine receptor channels. Effects on IP3 receptor channels are both direct and indirect via elevation of IP3 levels.

Original languageEnglish (US)
Pages (from-to)207-215
Number of pages9
JournalAnesthesiology
Volume95
Issue number1
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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