LACK OF CYSTIC-FIBROSIS TRANSMEMBRANE REGULATOR-TYPE CHLORIDE CURRENTIN PEDIATRIC HUMAN ATRIAL MYOCYTES

Mature cardiomyocytes have been shown to possess a cyclic AMP-mediated chloride channel (I-Cl) which is the product of the cystic fibrosis t ransmembrane regulator (CFTR) gene. Species variability has been demon strated for other ion channels. This study was designed to evaluate hu man I-Cl regulation using the whole-cell patch-clamp bioassay. Atrial tissue obtained from children undergoing congenital heart surgery was enzymatically dispersed into isolated myocytes. The patients ranged in age from 1 day to 11 years (mean 2 years). Isoproterenol was used to activate the cAMP second-messenger system in a potassium-free environm ent. Membrane calcium and sodium channels were pharmacologically block ed. Of 20 human atrial myocytes obtained from 13 pediatric patients, 8 0% had a small basal chloride current. The current could be inhibited by the anion transport blocker, 9-anthracene carboxylic acid. In 4 of 20 otherwise viable myocytes, no I-Cl could be elicited, either at bas eline or with beta-adrenergic stimulation. Of the 16 myocytes with a b asal I-Cl, the current was unaffected by cAMP stimulation in 15 (94%) cells. There were no significant differences in age, gender or clinica l status of patients whose cells conducted Cl- current compared with p atients whose myocytes had no measurable I-Cl. Ten mature guinea pig v entricular myocytes were evaluated using the same whole-cell patch-cla mp technique. Seven of 10 cells showed a reversible increase in I-Cl w ith isoproterenol exposure. Despite presence of the CFTR gene in human cardiomyocytes, functional expression of the cAMP-activated I-Cl does not appear evident in isolated pediatric atrial myocytes. Whether the pathophysiology of congenital heart disease may influence chloride cu rrent modulation via alterations in adrenergic tone, intracellular Ca2 + regulation, and cellular osmotic conditions remains to be establishe d.