Optical imaging of large-scale correlated wave activity in the developing rat CNS.

A simulation of the rat distal convoluted tubule (DCT) is completed with a model of the late portion, or connecting tubule (CNT). This CNT model is developed by relying on a prior cortical collecting duct (CCD) model (Weinstein AM. Am J Physiol Renal Physiol 280: F1072-F1092, 2001), and scaling up transport activity of the three cell types to a level appropriate for DCT. The major difference between the two tubule segments is the lower CNT water permeability. In early CNT the luminal solution is hypotonic, with a K(+) concentration less than that of plasma, and it is predicted that osmotic equilibration requires the whole length of CNT, to end with a nearly isotonic fluid, whose K(+) concentration is severalfold greater than plasma. With respect to potassium secretion, early CNT conditions are conducive to maximal fluxes, whereas late conditions require the capacity to transport against a steep electrochemical gradient. The parameter dependence for K(+) secretion under each condition is different: maximal secretion depends on luminal membrane K(+) permeability, but the limiting luminal K(+) concentration does not. However, maximal secretion and the limiting gradient are both enhanced by greater Na(+) reabsorption. While higher CNT water permeability depresses K(+) secretion, it favors Na(+) reabsorption. Thus in antidiuresis there is a trade-off between enhanced Na(+)-dependent K(+) secretion and the attenuation of K(+) secretion by slow flow. When the CNT model is configured in series with the early DCT, thiazide diuretics promote renal K(+) wasting by shifting Na(+) reabsorption from early DCT to CNT; they promote alkalosis by shifting the remaining early DCT Na(+) reabsorption to Na(+)/H(+) exchange. This full DCT is suitable for simulating the defects of hyperkalemic hypertension, but the model offers no suggestion of a tight junction abnormality that might contribute to the phenotype.