Inner-medullary organic osmolytes and inorganic electrolytes in K depletion

The renal concentrating defect typical for chronic K depletion has been asc ribed to malfunction of; renomedullary cells caused by inadequate accumulat ion of organic osmolytes. A reduction in intracellular ionic strength, whic h is believed to influence decisively the accumulation of organic osmolytes , has been held responsible for insufficient osmolyte accumulation. To test this hypothesis, intra- and extracellular Na, Cl and K concentrations, the major determinants of ionic strength, were measured in the papilla by elec tron microprobe analysis and organic osmolytes (glycerophosphorylcholine, b etaine, sorbitol, myo-inositol, free amino acids) in inner-medullary tissue by HPLC in antidiuretic rats kept on either a control (normal-K) or a K-de plete (low-K) diet and in euhydrated rats with free access to water and con trol diet. K depletion was associated with a reduced urine concentrating ab ility. Papillary interstitial ionic strength (sum of Na, Cl and K) in antid iuretic low-K rats was significantly reduced compared with antidiuretic nor mal-K rats (688+/-19 vs. 971+/-61 mmol/kg wet wt) but was similar to that i n euhydrated normal-K rats (643+/-35 mmol/kg wet wt). The lower interstitia l ionic strength in antidiuretic low-K and euhydrated normal-K rats was ass ociated with a lower total content of organic osmolytes in the inner medull a (365+/-14 and 381+/-20, respectively, vs. 465+/-11 mmol/kg protein in ant idiuretic normal-K rats). Intracellular ionic strength (sum of Na, Cl and K ) of papillary collecting duct cells, however, was similar in antidiuretic normal-K and euhydrated normal-K rats (171+/-5 and 179+/-11 mmol/kg wet wt) but lower in antidiuretic low-K rats (138+/-9 mmol/kg wet wt). These resul ts do not support the view that, in the steady state of osmotic adaptation of renomedullary cells in situ, intracellular ionic strength is the decisiv e factor for maintaining high levels of organic osmolytes. During chronic K depletion, reduced osmolyte accumulation by renomedullary cells may be the consequence, rather than the cause, of lower medullary interstitial tonici ty.