VOLATILE ANESTHESIC INHIBITION OF CA++ RELEASE IN AIRWAY

  • Sieck, Gary C (PI)

Project: Research project

Project Details

Description

DESCRIPTION: (Adapted from the abstract)
The long-term goals of the proposed research are to understand the
effects of volatile anesthetics on: 1) the regulation of [Ca2+]i; 2) the
coupling between elevated [Ca2+]i and mechanical responses (excitation-
contraction); and 3) the Ca2+ sensitivity of force generation in ASM
cells. The proposed studies will use real-time confocal microscopy to
examine the effects of halothane and sevoflurane on acetylcholine-
induced [Ca2+]i oscillations in localized regions within freshly
dissociated porcine ASM cells. Flash photolytic release of caged Ca2+
and ATP will be used to determine effects of volatile anesthetics on the
intracellular process contributing to the delays during excitation-
contraction coupling. There are four major specific aims in the proposed
studies: 1) To determine the effect of volatile anesthetics on
acetylcholine-induced [Ca2+]i oscillations, 2) To determine whether
volatile anesthetics affect second messenger (IP3, and cADPR) production
in response to acetylcholine, 3) To determine whether volatile
anesthetics affect IP3 and cADPR-mediated SR Ca2+ release, and 4) To
determine the effects of volatile anesthetic on the Ca2+ sensitivity of
force generation and the dynamic coupling between elevated [Ca2+]i and
ASM contraction. With regard to [Ca2+]i regulation, the authors
hypothesize that volatile anesthetics 1) increase IP3 production but
decrease cADPR production; 2) decrease SR Ca2+ content via an IP3-
induced "leak" and reduced SR Ca2+ reuptake, thereby decreasing the peak
amplitude of [Ca2+]i oscillations; and 3) lower the sensitivity of Ca2+-
induced Ca2+ release (CICR) via decreased cADPR production, thereby
slowing [Ca2+]i oscillation frequency and propagation velocity. With
regard to the coupling between elevated [Ca2+]i and ASM contraction, the
investigators hypothesize that volatile anesthetics 1) decrease the
steady-state Ca2+ sensitivity of force generation during muscarinic
stimulation and 2) delay excitation-contraction coupling.
StatusFinished
Effective start/end date1/1/9912/31/07

ASJC

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)