Chloride channels of skeletal muscle from developing, adult and aged rats are differently affected by enantiomers of 2-(p-chlorophenoxy) propionic acid

Abstract

Enantiomers of 2-(p-chlorophenoxy) propionic acid, compounds acting specifically on chloride channels of adult rat skeletal muscles, have been tested on extensor digitorum longus (EDL) muscle of developing and aged rats, in an attempt to characterize the chloride channels responsible for the low chloride conductance (GCl) found in the above physiological situations. The S-(-) enantiomer, which produces a concentration-dependent inhibition of GCl in the adult EDL, is less effective in inhibiting GCl of EDL of either 2-3 weeks or 29 months old rats, particularly at low concentrations. The R-(+) isomer, which in the adult enhances GCl at low concentrations and blocks it at concentrations higher than 10 microM, lacks inhibitory action, enhancing GCl in both developing and aged EDL. At 30-40 days of age both the enantiomers produce almost the same effects exerted in adulthood. From these data we hypothesize that the low GCl found in EDL of developing and aged rats might be due not only to a lower number of conductive channels but also to the presence of a mixed population of isoforms of chloride channels having different pharmacological properties.