The effects of halothane pretreatment on manganese influx induced by muscarinic stimulation of airway smooth muscle

David Oman Warner, Keith A. Jones, Robert R. Lorenz

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We hypothesized that halothane inhibits contraction of canine airway smooth muscle in part by depleting sarcoplasmic reticulum (SR) calcium stores, which affects subsequent force and calcium influx. This hypothesis was tested by using the rate of quenching of fura-2 fluorescence by manganese (Mn2+) as an index of calcium influx. When added 10 min before submaximum muscarinic stimulation (with 0.3 μM acetylcholine [ACh]), halothane (0.60 ± 0.04 mM [mean ± sE]) reduced subsequent isometric force and intracellular calcium concentration ([Ca2+](i)) measured 10 min after contraction (to 55% ± 5% and 69% ± 4% of control, respectively). The Mn2+ influx measured concurrently was significantly increased by halothane (by 57% ± 22%). Depletion of SR calcium stores by ACh prior to contraction also increased Mn2+ influx (by 46% ± 6%) but did not affect developed force or increase [Ca2+](i) in response to submaximum muscarinic stimulation. Halothane did not affect [Ca2+](i) or Mn2+ influx when added prior to maximum stimulation with 100 μM ACh but significantly reduced developed force. These findings are consistent with the hypothesis that halothane-induced SR depletion prior to contraction stimulates subsequent calcium influx, but they further suggest that halothane-induced SR depletion itself does not contribute significantly to the reduction in contractility produced by halothane in the canine airway smooth muscle.

Original languageEnglish (US)
Pages (from-to)1366-1371
Number of pages6
JournalAnesthesia and Analgesia
Volume84
Issue number6
DOIs
StatePublished - 1997

Fingerprint

Halothane
Manganese
Cholinergic Agents
Smooth Muscle
Sarcoplasmic Reticulum
Calcium
Acetylcholine
Canidae
Fura-2
Fluorescence

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

The effects of halothane pretreatment on manganese influx induced by muscarinic stimulation of airway smooth muscle. / Warner, David Oman; Jones, Keith A.; Lorenz, Robert R.

In: Anesthesia and Analgesia, Vol. 84, No. 6, 1997, p. 1366-1371.

Research output: Contribution to journalArticle

@article{dfc45afad99a4f6a933dbb37027baf29,
title = "The effects of halothane pretreatment on manganese influx induced by muscarinic stimulation of airway smooth muscle",
abstract = "We hypothesized that halothane inhibits contraction of canine airway smooth muscle in part by depleting sarcoplasmic reticulum (SR) calcium stores, which affects subsequent force and calcium influx. This hypothesis was tested by using the rate of quenching of fura-2 fluorescence by manganese (Mn2+) as an index of calcium influx. When added 10 min before submaximum muscarinic stimulation (with 0.3 μM acetylcholine [ACh]), halothane (0.60 ± 0.04 mM [mean ± sE]) reduced subsequent isometric force and intracellular calcium concentration ([Ca2+](i)) measured 10 min after contraction (to 55{\%} ± 5{\%} and 69{\%} ± 4{\%} of control, respectively). The Mn2+ influx measured concurrently was significantly increased by halothane (by 57{\%} ± 22{\%}). Depletion of SR calcium stores by ACh prior to contraction also increased Mn2+ influx (by 46{\%} ± 6{\%}) but did not affect developed force or increase [Ca2+](i) in response to submaximum muscarinic stimulation. Halothane did not affect [Ca2+](i) or Mn2+ influx when added prior to maximum stimulation with 100 μM ACh but significantly reduced developed force. These findings are consistent with the hypothesis that halothane-induced SR depletion prior to contraction stimulates subsequent calcium influx, but they further suggest that halothane-induced SR depletion itself does not contribute significantly to the reduction in contractility produced by halothane in the canine airway smooth muscle.",
author = "Warner, {David Oman} and Jones, {Keith A.} and Lorenz, {Robert R.}",
year = "1997",
doi = "10.1097/00000539-199706000-00035",
language = "English (US)",
volume = "84",
pages = "1366--1371",
journal = "Anesthesia and Analgesia",
issn = "0003-2999",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - The effects of halothane pretreatment on manganese influx induced by muscarinic stimulation of airway smooth muscle

AU - Warner, David Oman

AU - Jones, Keith A.

AU - Lorenz, Robert R.

PY - 1997

Y1 - 1997

N2 - We hypothesized that halothane inhibits contraction of canine airway smooth muscle in part by depleting sarcoplasmic reticulum (SR) calcium stores, which affects subsequent force and calcium influx. This hypothesis was tested by using the rate of quenching of fura-2 fluorescence by manganese (Mn2+) as an index of calcium influx. When added 10 min before submaximum muscarinic stimulation (with 0.3 μM acetylcholine [ACh]), halothane (0.60 ± 0.04 mM [mean ± sE]) reduced subsequent isometric force and intracellular calcium concentration ([Ca2+](i)) measured 10 min after contraction (to 55% ± 5% and 69% ± 4% of control, respectively). The Mn2+ influx measured concurrently was significantly increased by halothane (by 57% ± 22%). Depletion of SR calcium stores by ACh prior to contraction also increased Mn2+ influx (by 46% ± 6%) but did not affect developed force or increase [Ca2+](i) in response to submaximum muscarinic stimulation. Halothane did not affect [Ca2+](i) or Mn2+ influx when added prior to maximum stimulation with 100 μM ACh but significantly reduced developed force. These findings are consistent with the hypothesis that halothane-induced SR depletion prior to contraction stimulates subsequent calcium influx, but they further suggest that halothane-induced SR depletion itself does not contribute significantly to the reduction in contractility produced by halothane in the canine airway smooth muscle.

AB - We hypothesized that halothane inhibits contraction of canine airway smooth muscle in part by depleting sarcoplasmic reticulum (SR) calcium stores, which affects subsequent force and calcium influx. This hypothesis was tested by using the rate of quenching of fura-2 fluorescence by manganese (Mn2+) as an index of calcium influx. When added 10 min before submaximum muscarinic stimulation (with 0.3 μM acetylcholine [ACh]), halothane (0.60 ± 0.04 mM [mean ± sE]) reduced subsequent isometric force and intracellular calcium concentration ([Ca2+](i)) measured 10 min after contraction (to 55% ± 5% and 69% ± 4% of control, respectively). The Mn2+ influx measured concurrently was significantly increased by halothane (by 57% ± 22%). Depletion of SR calcium stores by ACh prior to contraction also increased Mn2+ influx (by 46% ± 6%) but did not affect developed force or increase [Ca2+](i) in response to submaximum muscarinic stimulation. Halothane did not affect [Ca2+](i) or Mn2+ influx when added prior to maximum stimulation with 100 μM ACh but significantly reduced developed force. These findings are consistent with the hypothesis that halothane-induced SR depletion prior to contraction stimulates subsequent calcium influx, but they further suggest that halothane-induced SR depletion itself does not contribute significantly to the reduction in contractility produced by halothane in the canine airway smooth muscle.

UR - http://www.scopus.com/inward/record.url?scp=0030966198&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030966198&partnerID=8YFLogxK

U2 - 10.1097/00000539-199706000-00035

DO - 10.1097/00000539-199706000-00035

M3 - Article

C2 - 9174322

AN - SCOPUS:0030966198

VL - 84

SP - 1366

EP - 1371

JO - Anesthesia and Analgesia

JF - Anesthesia and Analgesia

SN - 0003-2999

IS - 6

ER -