Abnormalities in membrane microviscosity and ion transport in genetic muscular dystrophy.

Abstract

WE have demonstrated recently several functional differences between membrane-bound enzymes from tissues of muscular dystrophic chicks and of controls1. Several other membrane anomalies have been associated with this disease2–7, but so far the only known biochemical anomaly in the affected membranes is a difference in lipid composition8,9. This could cause all the observed functional defects, including those in enzyme activities and permeability, through an alteration in the membrane microenvironment10. Certain physical properties of the microenvironment can be studied by fluorescent polarisation techniques that measure the mobility of a lipid-soluble fluorescent dye11,12. The basis for this approach is the fact that membrane cholesterol, which strongly affects the microviscosity of liposomes10, is present in significantly greater than normal amounts in genetic muscular dystrophy. Using this approach, we found (Table 1) that the membranes of muscle, liver and erythrocytes of dystrophic chicks have a significantly higher microviscosity than normal controls. The greatest difference was in muscle, the site of the clinical symptoms of this genetic disease. The higher cholesterol :phospholipid ratio characteristic of the diseased membrane is sufficient to account for the observed increase in microviscosity11.