Cell volume increases of physiologic amplitude activate basolateral K and Cl conductances in the rabbit proximal convoluted tubule

Abstract

The effects of increases in cell volume (CV) of physiologic amplitude, induced either hypotonically or isotonically, were studied on the three major basolateral conductances of rabbit isolated proximal convoluted tubules. CV increases were produced by a 40 mosmol/kg H2O hypotonic shock or by the isotonic replacement of mannitol by 40 mM glucose or alanine. The hypotonic shock led to an increase in CV of 17 ± 3% (N = 8), whereas additions of glucose and alanine led to increases in CV of 22.6 ± 2.5% (N = 7) and 28.3 ± 3.5 (N = 5) respectively. Under all of these conditions, the absolute conductance mediated by the NaHCO3 cotransporter did not vary appreciably. This allowed determination of the variations of the absolute conductances to potassium (G(K)) and chloride (G(Cl)) from their measured partial conductances. All three protocols induced significant increases in G(K) by factors of 2,37 ±. 0.3. 1.43 ± 0.16, and 1.69 ± 0.40, and in G(Cl) by factors of 3.32 ±0.57.3.68 ± 0.75, and 3.90 ± 1.0 during the hypotonic, glucose, and alanine protocols, respectively. These increases in G(K) and G(Cl) occurred with a delay compared with the variations in CV, indicating a more elaborate signaling mechanism than stretch-activation of channels that are known to activate channels within seconds. Intracellular pH increased from 7.19 ± 0,03 to 7.23 ± 0.03, 7.17 ± 0.02 to 7.20 ± 0.02, and 7.13 ± 0.01 to 7.16 ± 0.01 after the hypotonic shock and the glucose and alanine additions, respectively. The study presented here demonstrates that there is a close relationship between CV and G(K) and G(Cl), independent of the means used (hypotonically or isotonically) to increase CV in rabbit proximal convoluted tubules. CV activation of G(K) is proposed to account for part of the increase in G(K) reported previously during activation of transepithelial transport.