Peptide hormones and adrenergic agents probably act on target cells only if there is a specific receptor on the cell surface. Information that such a receptor, or group of receptors, is occupied by an appropriate agent is transmitted to other portions of the membrane and to the cell interior; there ensues a constellation of characteristic effects. The unknown information transfer is called transduction. Among candidate transducers is the electrical field strength through the membrane, a possibility we first suggested in 1972. Reports agree that peptide hormones and catecholamines change transmembrane potential; some hyperpolarize, some depolarize. Insulin hyperpolarizes rat skeletal muscle. The goal of this proposal is to test the hypothesis that altered electrical field strength is a transducer of hormone action. Three requirements are: (1) hormone-induced altered electrical field strength must be rapid, preceding effector responses; (2) altered field strength alone, produced by applied voltage in the absence of hormone, must mimic several of the hormone responses; (3) prevention of hormone-induced altered field strength must prevent responses to the hormone. This proposal includes studies of all three requirements in rat caudofemoralis muscle, mainly concerning hyperpolarization as a transducer of insulin action. The major novel method uses a device that produces small hyperpolarization or depolarization over a 4mm-long segment of a whole muscle. Studies will be extended to other hormones that alter muscle membrane potential, to possible relations between altered polarization and other events in the transduction chain, and to the mechanisms by which altered membrane potential transduces the signal from the hormone-receptor site.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK017574-12
Application #
3225784
Study Section
Metabolism Study Section (MET)
Project Start
1974-05-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
12
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Zierler, K; Wu, F S (1992) An early outward transient K+ current that depends on a preceding Na+ current and is enhanced by insulin. Pflugers Arch 422:267-72
Zierler, K (1989) Misuse of nonlinear Scatchard plots. Trends Biochem Sci 14:314-7