DEVELOPMENTAL-CHANGES OF MEMBRANE ELECTRICAL-PROPERTIES OF RAT SKELETAL-MUSCLE FIBERS PRODUCED BY PRENATAL EXPOSURE TO CARBON-MONOXIDE

The effects of prenatal exposure to 75 and 150 ppm of carbon monoxide (CO) were evaluated in vitro on the electrical parameters of extensor digitorum longus muscle of newborn rats, by means of computerized two intracellular microelectrode technique. Within the first 2 months of p ostnatal life the muscles from offspring of mothers exposed to 150 ppm CO showed lower values of resting chloride conductance (G(Cl)) with r espect to age-matched controls, but no significant differences were re corded after 80 days of life. Between 40-200 days of rife, the extenso r digitorum longus muscles from offspring of 150 ppm CO exposed rats s howed a pharmacological response to a specific chloride channel modula tor, the R-(+)-enantiomer of 2-( p-chlorophenoxy)propionic acid(R-(+)- CPP), different from that of age-matched controls, but similar to that of normal developing rats aged 8-20 days. The prenatal exposure to 15 0 ppm CO also slightly delayed the developmental reduction of resting potassium conductance (G(K)); indeed higher Values of G(K) were record ed with respect to controls until 60 days of postnatal life. In the of fspring of 150 ppm CO treated rats a slight and reversible modificatio n of the excitability parameters related to G(Cl) were also observed a long with a decreased sensitivity to tetrodotoxin. In the muscle from offspring of 75 ppm CO treated animals G(Cl) and G(K) were not differe nt with respect to controls, at any age; however the pharmacological m odulation of G(Cl) by R-(+)-CPP was similar to that observed in the ra ts prenatally exposed 150 ppm CO. These results suggest that the prena tal exposure to mild concentrations of CO produces developmental alter ations of the ion channels responsible for the passive and active memb rane electrical properties of rat skeletal muscle fibers.