Ion transport plays an essential role in the maintenance of lens volume and transparency. The long-term goal of this research is to produce a detailed model of lens ion transport that could be used to understand the mechanisms of some types of cataracts. The model will require the details of the individual ion transport processes and their control in each of the cell types in the lens. Using a combination of cell culture and patch technology it is possible to look at the molecular details of conductive ionic transport pathways. Recent experiments on lens epithelial cells have identified three main types of potassium conductances: 1) a delayed rectifier, 2) an inward rectifier and 3) a calcium-activated potassium conductance. It is the hypothesis of this grant that the lens inwardly rectifying potassium conductance functions in setting resting voltage and perhaps buffering extracellular and recycling intracellular potassium. The inward rectifier may also be involved in the process of fiber cell formation. It is the primary objective of this grant to test this hypothesis and characterize the biophysical properties and physiological control mechanisms of this inward rectifier. Biophysical characterization will include description of gating and permeation properties. Measurements of gating will address the issues of allosteric control of the channel by potassium and the mechanism of rectification. Permeation studies will be aimed at finding and characterizing blockers for the channel. Experiments are included that will examine the molecular basis of second messenger control of the inward rectifier and determine if any of the known primary messengers that control inward rectifiers in other tissues or that control lens potassium conductance have effects on the lens inward rectifier. The role of the inward rectifier in setting resting voltage will be determined using blockers and the potassium dependence of the current. Measurements of the biophysical properties and cellular distribution within the lens will be used in assessing the role of the inward rectifier in other functions.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29EY009636-04
Application #
2163313
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1991-09-01
Project End
1996-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Arizona State University-Tempe Campus
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
188435911
City
Tempe
State
AZ
Country
United States
Zip Code
85287
Cokmus, C; Davidson, E W; Cooper, K (1997) Electrophysiological effects of Bacillus sphaericus binary toxin on cultured mosquito cells. J Invertebr Pathol 69:197-204
Crimando, J; Cooper, K; Hoffman, S A (1997) Inhibition of sodium channel currents by antineuronal autoantibody from autoimmune mice. Ann N Y Acad Sci 823:303-7
O'Grady, S M; Cooper, K E; Rae, J L (1993) Regulation of a voltage-dependent, calcium-activated K conductance by cyclic GMP in dissociated flounder enterocytes. J Comp Physiol B 163:581-6
Cooper, K; Watsky, M; Rae, J (1992) Potassium currents from isolated frog lens epithelial cells. Exp Eye Res 55:861-8