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 postnatal life the muscles from offspring of mothers exposed to 150 ppm CO showed lower values of resting chloride conductance (G(Cl)) with respect to age-matched controls, but no significant differences were recorded after 80 days of life. Between 40-200 days of rife, the extensor digitorum longus muscles from offspring of 150 ppm CO exposed rats showed a pharmacological response to a specific chloride channel modulator, 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 150 ppm CO also slightly delayed the developmental reduction of resting potassium conductance (G(K)); indeed higher Values of G(K) were recorded with respect to controls until 60 days of postnatal life. In the offspring of 150 ppm CO treated rats a slight and reversible modification of the excitability parameters related to G(Cl) were also observed along with a decreased sensitivity to tetrodotoxin. In the muscle from offspring of 75 ppm CO treated animals G(Cl) and G(K) were not different with respect to controls, at any age; however the pharmacological modulation of G(Cl) by R-(+)-CPP was similar to that observed in the rats prenatally exposed 150 ppm CO. These results suggest that the prenatal exposure to mild concentrations of CO produces developmental alterations of the ion channels responsible for the passive and active membrane electrical properties of rat skeletal muscle fibers.