Diluting power of thick limbs of Henle. I. Peritubular hypertonicity blocks basolateral Cl- channels

This paper provides the results of experiments intended to assess the mechanism responsible for the suppression of net salt absorption and the attendant spontaneous voltage (Ve, mV) that occurs when isolated thick ascending limbs of Henle (TAL) are exposed to a hypertonic environment. In isolated mouse medullary (MTAL) and cortical (CTAL) segments, as well as in rabbit MTAL segments, increases in peritubular osmolality with urea produced a graded suppression of Ve. This effect was evaluated in further detail in isolated mouse MTAL segments, where 600 mM peritubular urea produced a reversible reduction in Ve and a reversible reduction in the transcellular electrical conductance (Gc; mS.cm-2). There was no detectable effect on the paracellular conductance (Gs; mS.cm-2). Simultaneously, 600 mM peritubular urea also produced hyperpolarization of the voltage across basolateral membranes (mV). Moreover, 600 mM peritubular urea produced virtually the same magnitude reduction in Gc either in the absence or presence of 10(-4) M luminal furosemide. Thus we conclude that peritubular urea hypertonicity directly suppresses the Cl- conductance of basolateral membranes (mS.cm-2).