TY - JOUR
T1 - Effect of halothane on intracellular calcium oscillations in porcine tracheal smooth muscle cells
AU - Pabelick, Christina M.
AU - Prakash, Y. S.
AU - Kannan, Mathur S.
AU - Jones, Keith A.
AU - Warner, David O.
AU - Sieck, Gary C.
PY - 1999/1
Y1 - 1999/1
N2 - The effect of halothane on intracellular Ca2+ concentration ([Ca2+](i)) regulation in porcine tracheal smooth muscle cells was examined with real-time confocal microscopy. Both 1 and 2 minimum alveolar concentration (MAC) halothane increased basal [Ca2+](i) when Ca2+ influx and efflux were blocked, suggesting increased sarcoplasmic reticulum (SR) Ca2+ leak and/or decreased reuptake. In β-escin-permeabilized cells, heparin inhibition of inositol 1,4,5-trisphosphate-receptor channels blunted the halothane-induced increase in [Ca2+](i). Both 1 and 2 MAC halothane decreased the frequency and amplitude of ACh-induced [Ca2+](i) oscillations (which represent SR Ca2+ release through ryanodine-receptor channels), abolishing oscillations in ~20% of tracheal smooth muscle cells at 2 MAC. When Ca2+ influx and efflux were blocked, halothane increased the baseline and decreased the frequency and amplitude of [Ca2+](i) oscillations, inhibiting oscillations in ~70% of cells at 2 MAC. The fall time of [Ca2+](i) oscillations and the rate of fall of the [Ca2+](i) response to caffeine were both increased by halothane. These results suggest that halothane abolishes agonist-induced [Ca2+](i) oscillations by 1) depleting SR Ca2+ via increased Ca2+ leak through inositol 1,4,5-trisphosphate- receptor channels, 2) decreasing Ca2+ release through ryanodine-receptor channels, and 3) inhibiting reuptake.
AB - The effect of halothane on intracellular Ca2+ concentration ([Ca2+](i)) regulation in porcine tracheal smooth muscle cells was examined with real-time confocal microscopy. Both 1 and 2 minimum alveolar concentration (MAC) halothane increased basal [Ca2+](i) when Ca2+ influx and efflux were blocked, suggesting increased sarcoplasmic reticulum (SR) Ca2+ leak and/or decreased reuptake. In β-escin-permeabilized cells, heparin inhibition of inositol 1,4,5-trisphosphate-receptor channels blunted the halothane-induced increase in [Ca2+](i). Both 1 and 2 MAC halothane decreased the frequency and amplitude of ACh-induced [Ca2+](i) oscillations (which represent SR Ca2+ release through ryanodine-receptor channels), abolishing oscillations in ~20% of tracheal smooth muscle cells at 2 MAC. When Ca2+ influx and efflux were blocked, halothane increased the baseline and decreased the frequency and amplitude of [Ca2+](i) oscillations, inhibiting oscillations in ~70% of cells at 2 MAC. The fall time of [Ca2+](i) oscillations and the rate of fall of the [Ca2+](i) response to caffeine were both increased by halothane. These results suggest that halothane abolishes agonist-induced [Ca2+](i) oscillations by 1) depleting SR Ca2+ via increased Ca2+ leak through inositol 1,4,5-trisphosphate- receptor channels, 2) decreasing Ca2+ release through ryanodine-receptor channels, and 3) inhibiting reuptake.
KW - Airway
KW - Muscarinic receptor
KW - Sarcoplasmic reticulum
KW - Volatile anesthetic
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U2 - 10.1152/ajplung.1999.276.1.l81
DO - 10.1152/ajplung.1999.276.1.l81
M3 - Article
C2 - 9887059
AN - SCOPUS:0032917061
SN - 1040-0605
VL - 276
SP - L81-L89
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 1 20-1
ER -