VOLATILE ANESTHESIC INHIBITION OF CA++ RELEASE IN AIRWAY

  • Sieck, Gary C, (PI)

Project: Research project

Project Details

Description

DESCRIPTION: 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

Funding

  • National Institutes of Health: $257,870.00
  • National Institutes of Health
  • National Institutes of Health: $252,325.00
  • National Institutes of Health: $325,580.00
  • National Institutes of Health: $359,160.00
  • National Institutes of Health: $33,580.00
  • National Institutes of Health: $285,138.00
  • National Institutes of Health: $292,000.00
  • National Institutes of Health: $263,582.00

ASJC

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

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