Henry Joseph Binder MD
Professor Emeritus of and Senior Research Scientist in Medicine (Digestive Diseases)
ATPase; Colonic Electrolyte Transport; Epithelial Cell Function; Ion Transport; Short Chain Fatty Acids; Molecular Cellular Entities; Receptors
Regulation of colonic Na transport in apical and basolateral membranes.
The goal of our research program is to further the understanding of the regulation of colonic electrolyte transport; the clinical expression of these studies is an increased knowledge of the pathophysiology of and improved treatment for diarrheal disorders.
One area of research is the cellular mechanisms of active potassium absorptive and secretory processes in the colon. Primary emphasis at the present time is directed toward active K absorption which is energized by apical membrane H,K-ATPase, a member of the gene family of P-type ATPases. The molecular regulation of H,K-ATPase is being actively studied as well as the mechanism of the enhanced K absorption induced by both aldosterone and dietary K depletion. The role of basolateral K-Cl cotransport is also critical in active K absorption.
In collaboration with my colleagues Drs Geibel and Rajendran we also have explored the unique features of colonic crypt cell function. These studies in the isolated perfused colonic crypt have established that colonic crypts absorb fluid and Na in the basal state as a result of a novel Na-H exchange (NHE) that is Cl-dependent (Cl-NHE). This Cl-NHE is unique and its cloning is in progress. The isolated colonic crypt also provides a much needed model system to study colonic HCO3 secretion. Recent studies indicate that colonic HCO3 secretion is closely linked to Cl secretion but does not involve an apical membrane Cl-HCO3 exchange.
A final area of present interest is the identification of the cellular mechanism of absorption of short chain fatty acids (SCFA), the primary anion in stool, and their stimulation of Na-Cl absorption in the colon. SCFA stimulation of Na-Cl absorption involves an apical membrane mechanism of SCFA uptake (SCFA-HCO3 exchange) as well as Na-H and Cl-SCFA exchanges. The unexpected failure of cyclic nucleotides to inhibit SCFA stimulation of Na-Cl absorption led to the hypothesis that starch that is relatively resistant to pancreatic amylase digestion could serve as an adjunct to oral rehydration therapy (ORT) in the treatment of diarrhea by enhancing colonic SCFA production that in turn would result in increased fluid and Na absorption. This was established in recent clinical trials of patients with cholera at Christian Medical College in Vellore, India. Further trials are in progress and planned to establish the optimal resistant starch formulation for ORT and optimal circumstances for its use.