Effects of mineralocorticoids on transport properties of cortical collecting duct basolateral membrane

Abstract

The effects of long-term mineralocorticoid (deoxycorticosterone acetate, DOCA) elevation for 9-16 days on the active and passive transport properties of the basolateral cell membrane of rabbit cortical collecting ducts were assessed using microelectrode techniques. It was found that both the transepithelial membrane voltage (Vte) and basolateral membrane voltage (Vb) hyperpolarized and the basolateral membrane conductance (Gb) increased on chronic elevation of mineralocorticoid levels. Barium (5 mM) addition to the bathing solution effectively blocked an induced K+ current across the basolateral cell membrane without an immediate affect on the other barriers. Therefore Ba2+ was used to quantitate the basolateral cell membrane K+ conductance (GbK). It was found that GbK increased from 1.0 +/- 0.2 mS X cm-2 (controls) to 3.7 +/- 1.0 mS X cm-2 in DOCA-treated animals. The basolateral membrane electrogenic pump current (Ibact) was quantitated from the change in the basolateral membrane equivalent emf on addition of either ouabain (0.1 mM) to the bath or of amiloride (50 microM) to the perfusate. There was a large increase in Ibact from 32 microA X cm-2 in controls to 195 microA X cm-2 in the DOCA-treated group. In addition, the estimated Na+-to-K+ coupling ratio of the Na+ pump was observed to increase from 1.6 to 1.0 in the control group to 3.2 to 1.0 in the DOCA-treated group. The estimated basolateral membrane passive K+ current (IbK) increased from a value that was not significantly different from 0 in controls to approximately -45 microA X cm-2 (from bath to cell) in the DOCA-treated group. These findings support a model whereby mineralocorticoids induce an increase in electrogenic Na+ pump activity in response to chronically elevated rates of Na+ transport. This results in a hyperpolarization of Vb, which is well above EbK, thereby resulting in a net driving force for K+ uptake into the cell, bringing about an increased rate of K+ secretion.