The long term objective of the proposed research project is to define the functional role of voltage gated Ca++ entry in skeletal muscle. Voltage and current clamp experiments will be carried out in isolated skeletal muscle from the frog with the cut fiber preparation in the vaseline gap technique. Myoplasmic Ca++ transients will be optically measured with Antipyrylazo III. Ionic currents, charge movement and changes in intracellular Ca++ concentration will be studied simultaneously. The slow Ca++ channel is located in the tubular system and it is too slow to be activated during a single action potential, however this is not the case for the recently described fast Ca++ channel. In initial experiments the effect of reducing external Ca++ on the Ca++ transient associated with the action potential will be investigated. In order to distinguish the activation of these channel in relation to charge movement and Ca++ transients, the pharmacology and modulation of fast and slow Ca++ channels will be studied in detail. In addition the recent described fast Ca++ channel will be further characterize in term of its localization, pharmacology and kinetic. These studies will be performed in a comparative way in preparations with variations of Ca++ channel currents such as the denervated muscle fiber, the end-plate region and the tail muscle from tadpoles. Ca++ channels were recently described in skeletal tonic fibers, where Ca++ entry may play a role in contraction. This point will be clarified by simultaneously measuring Ca++ currents, Ca++ transient and charge movement. An insight on the role of Ca++ channel activation will be obtained also from developmental studies, with measurements of Ca++ macroscopic and single currents that will be performed in primary cultures of skeletal muscle of new born rats. To define the physiological role of voltage gated Ca++ entry in skeletal muscle is a relevant problem in the medical sciences, since, Ca++ channel alterations have been recently described in muscle diseases such as muscular dysgenesis and muscle dystrophia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR038970-05
Application #
3159013
Study Section
Physiology Study Section (PHY)
Project Start
1987-09-01
Project End
1994-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
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