PHYSIOLOGY OF CALCIUM CHANNEL GENES

Project: Research project

Description

Calcium channels regulate a wide range of cellular activities.
Based on physiological and pharmacological evidence, diverse
calcium channel types exist and are presumably derived from
independent genes. The regulation of these calcium channel genes
during normal development and their effects on other genes are
poorly understood. This project utilizes naturally occurring
mutations in the calcium channel genes of vertebrates to gain
insights into the structure of calcium channels and the
modifications in electrophysiological and cellular functions that
ensue from the altered structures. Muscular dysgenesis (mdg) of
mice is a mutation in the gene for the alpha 1 subunit of the
skeletal muscle dihydropyridine (DHP) receptor and leads to loss
of normal calcium channels and excitation-contraction coupling.
However, dysgenic muscle does contain a low level of a mRNA
hybridizable with DHP receptor alpha 1 cDNA and also expresses an
unusual calcium current. Detailed molecular characterizations (via
cDNA cloning) of this DHP receptor mRNA from dysgenic muscle will
be carried out to obtain insights into the structural domains
within the normal DHP receptor which give rise to its
electrophysiological properties. Expression of the "dysgenic mRNA"
in heterologous systems and antisense RNA inhibition of expression
in dysgenic myotubes will be used to establish definitively whether
this mRNA encodes a novel calcium channel. The crooked neck dwarf
(cn) chicken and the cardiomyopathic (cm) hamster are known to
exhibit functional alterations in their calcium currents. These
mutants strains will be investigated along similar molecular
genetic lines to determine if the functional alterations arise from
mutations in the calcium channel genes in these mutants also.
Finally, the effects of the DHP receptor on the accumulation of
other mRNAs involved in muscle differentiation will be examined in
normal myotubes developing under experimental paralysis in culture. These multi-disciplinary and collaborative studies will provide
valuable new insights into the structure-function relationships,
and the regulation, of calcium channel genes.
StatusFinished
Effective start/end date7/1/895/31/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $116,567.00

Fingerprint

Calcium Channels
L-Type Calcium Channels
Genes
Muscles
Messenger RNA
Skeletal Muscle Fibers
Calcium
Antisense RNA
Excitation Contraction Coupling
Paralysis
Cricetinae
Vertebrates
Organism Cloning
Chickens
Neck
Complementary DNA
Pharmacology
Mutation

ASJC

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