The Role of Cortical Na,K-ATPase in Distal Nephron Potassium Secretion by the Immature Canine Kidney

Abstract

ABSTRACT. Amiloride-sensitive potassium secretion in response to acute potassium loading is lower in the newborn than in the adult. Potassium secretion is a function of late distal tubule and cortical collecting tubule Na,K-ATPase activity. Na,K-ATPase activity in vivo is determined by enzyme abundance and catalytic turnover. Chronic potassium supplementation increases potassium secretory capacity in the adult by increasing enzyme abundance in the late distal and cortical collecting tubules. We hypothesized that the lower potassium secretory capacity of the newborn was the result of lower late distal and cortical collecting tubule Na,K-ATPase activity and could be similarly enhanced. To test this hypothesis, newborn dogs were supplemented with 6 mmol KC1.d-'. kg-' for 1 wk; agematched litter mate controls were not ( n = 8 pairs). Potassium supplementation resulted in a mean increase in V,,, Na,K-ATPase activity in vitro (proportional to pump abundance) of 70 + 42%. Mean Na,K-ATPase activities + S E M were 279 + 58 versus 198 2 44 nmol inorganic P.h-I-gg DNA-', p = 0.05. However, amiloride-sensitive potassium secretion after an acute potassium load of 20 pmol. min-'. kg-' over 150 min was not enhanced (9.6 +-1.8 versus 8.9 + 0.8 pmol . min-' .kg-', potassium-supplemented versus control animals). We conclude that lower enzyme abundance is not primarily responsible for the newborn's lower potassium secretory capacity. W e speculate that the factor that limits secretion in the newborn during acute potassium loading does so by restricting catalytic turnover of the enzyme in vivo. (Pediatr Res 30: 457-463,1991) Abbreviations KIl2, substrate concentration at which the reaction velocity is half maximum Na,K-ATPase, sodium-potassium-activated adenosine triphosphatase T ' H~~, free water reabsorption TFK, tubular fluid potassium concentration TTKG, transtubular potassium gradient is less than that of the mature nephron (1). Transtubular potassium secretion in these nephron segments is driven by basolateral membrane Na,K-ATPase (2, 3). Na,K-ATPase activity has been shown to be lower in neonatal than adult nephron segments (4-6). It is possible, therefore, that the potassium secretory response of the immature nephron may be limited by lower Na,K-ATPase activity.Results of a study that examined the effect of increasing Na,KATPase activity on the renal response to acute potassium loading in newborn dogs did not support this possibility (7). In that study, newborn dogs were subjected to chronic potassium supplementation for 1 to 3 wk after birth to enhance Na,K-ATPase activity in potassium secretory nephron segment(s). Chronic potassium supplementation doubled V,,, cortical Na,K-ATPase activity compared with controls (who received distilled water supplementation), but did not enhance urinary excretion of an acute potassium load in the newborn dog. These results were interpreted to indicate that Na,K-ATPase pump abundance is not rate limiting in excretion of a potassium load in the newborn. However, it is possible that wate...

Should Scientists Bond with the Animals Whom They Use? Why Not?

“…chapter in The Inevitable Bond and Burghardt, 1991 ;Lorenz, 1991;and Bekoff & Allen, 1995), but I do not think that (i) anthropomorphic explanations are dangerous (Estep & Hetts, Chapter 2, p. 23), that (ii) the "dangers of anthropomorphism in science are widely known" (Estep & Hetts, p. 23) or broadly feared, or that(iii) …”