Regulation of Na/K-ATPase gene expression by thyroid hormone and hyperkalemia in the heart

Hypothermic hyperkalemic circulatory arrest has been widely used for myocar dial protection during heart surgery. Recent data showed that administratio n of triiodo-1-thyronine (T-3) postoperatively enhanced ventricular functio n. The effect of hyperkalemic arrest in conjunction with thyroid hormone on the plasma membrane enzyme sodium/potassium-adenosine triphosphatase (Na/K -ATPase), was determined in cultured neonatal rat atrial and ventricular my ocytes. Exposure of ventricular myocytes to hyperkalemic medium (50 mM KCI) in the absence of T-3 increased expression of the Na/K-ATPase catalytic su bunit mRNAs, alpha(1) and alpha(3) isoforms, by 1.9- and 1.5-fold, respecti vely (p < 0.01), which were accompanied by similar increases (1.4- and 1.8- fold) in protein content. Addition of T-3 to the hyperkalemic cultures atte nuated these increases in Na/K-ATPase mRNA isoforms to levels of expression observed in cells treated with T-3 (10(-8) M) alone. Similarly, expression of the alpha(1) mRNA isoform in atrial myocytes was increased (p < 0.05) b y hyperkalemic conditions, and T-3 treatment attenuated this effect. In con trast, although expression of the Na/K-ATPase beta(1) mRNA in both atrial a nd ventricular myocytes was significantly increased by hyperkalemia, additi on of T-3 did not prevent the hyperkalemic response, and in atrial myocytes T-3 significantly increased beta(1) mRNA expression 1.8-fold. These result s show that expression of cardiac Na/K-ATPase is regulated by T-3 and hyper kalemia in an isoform and chamber specific manner, and suggest that use of hyperkalemic cardioplegia during heart surgery may alter plasma membrane io n function.