Hypersodium absorption that causes impaired mucocilliary clearance is thought to be a major contributor to the pathophysiology of cystic fibrosis lung disease. Recent observations that proteases and protease inhibitors affect sodium transport rates in numerous epithelia has lead to suggestions that there is a intrinsic protease regulation of sodium transport in the lungs as well as other epithelia. However, the mechanism of this proposed regulation is unknown. We propose to use the method of noise analysis on sodium transporting epithelia and Xenopus oocytes as well as giant-patch patch-clamping to determine the transport parameters regulated by proteases. We will determine the necessary players in protease regulation of sodium transport. The methods we will use are less invasive and would provide highly detailed real time physiologically relevant data on sodium regulation by proteases and as such will provide a unique perspective on ion channel regulation With the data we hope to obtain, we can identify therapeutic targets specific for the protease regulation pathway that will reduce the severity of cystic fibrosis lung disease.
