and specific aims): Asthma is characterized by hypersensitivity of airway smooth muscle to spasmogens (acetylcholine (ACh), histamine (HIS) etc.). The underlying cause of this hypersensitivity is unknown. Spasmogens increase cytosolic Ca2+ concentration ([Ca2+]i) through the release of Ca2+ from the sarcoplasmic reticulum (SR), depolarization, and Ca2+ influx through voltage-activated channels and receptor-operated channels. The transient release of Ca2+ from the SR provides the trigger for the activation of a cascade of events which ultimately lead to cross-bridge cycling and tension development. The influx of extracellular Ca2+ appears to be involved in the refilling of the SR Ca2+ stores and tension maintenance. beta-adrenoceptor agonists, acting at b2 receptors, induce tracheal smooth muscle cell hyperpolarization, a decrease in Ca2+ influx and [Ca2+]i, and relaxation. The goal of this project is to characterize the interactions between the signal transduction pathways activated by beta-adrenoceptors and the spasmogens acetylcholine (ACh) and histamine (HIS) in isolated tracheal smooth muscle cells from swine.
The specific aims are to: 1) examine the role of KCa and KATP channels in the regulation of membrane potential (Vm) and [Ca2+]i in isolated swine tracheal smooth muscle cells; 2) characterize and compare spasmogen-induced changes in [Ca2+]i and the modulation of these effects on b-adrenoceptor activation; 3) characterize the pathways involved in the refilling of the SR Ca2+ store; 4) determine the effects of b-adrenoceptor activation on non-receptor-mediated IP3-induced oscillations in [Ca2+]i; and 5) examine the regulation of L-type Ca2+ channels by spasmogens and beta-adrenoceptor stimulation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL055547-02
Application #
2460175
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1996-08-01
Project End
2000-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Mississippi Medical Center
Department
Pharmacology
Type
Schools of Medicine
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216