Regulation of renal proximal tubule basolateral potassium channels.

In summary, these studies report a voltage-gated, stretch-activated K channel at the basolateral membrane of amphibian proximal tubule. In the normal range of potential, any reduction in metabolic activity leading to membrane depolarization would reduce the open-probability of the basolateral K channel, thereby preventing excessive loss of K out of the cell. This type of voltage gating is consistent with the decrease in macroscopic K conductance observed in perfused frog tubules after cell depolarization (Messner et al., 1985). However, it does not account for the delayed increase in basolateral K conductance that accompanies Na-substrate cotransport across the apical membrane. The stretch-activation property of basolateral K channels may explain both electrolyte and volume homeostasis in the amphibian proximal tubule. Na-substrate cotransport produces a gradual increase in cell volume in several preparations (Hempling and Hare 1961; Hacking and Eddy 1981; Hudson and Schultz 1988;). Hence, the observed increase in K conductance during luminal addition of Na-cotransported substrates may be mediated by small changes in cell volume. For example, a stretch-activated K channel, stimulated by a 1% increase in cell volume, would allow K to exit the cell down its electrochemical gradient, thereby balancing the increased K uptake associated with greater Na pump activity. A number of studies have provided evidence that cell swelling increases macroscopic K conductance (Davis and Finn 1982; Germann et al. 1986; Grinstein et al. 1982; Grinstein et al. 1984; Hamill 1983; Hoffmann 1985; Lau et al. 1984; Lopes and Guggino 1987; Richards and Dawson 1986) as well as chloride channel activity (Hudson and Schultz 1988). However, the present study is the first to suggest that the swelling-induced increase in basolateral K conductance results from stretch-activated K channels. This same stretch-activation property may also be involved in the VRD that occurs during exposure of proximal tubule cells to hypotonic media (Dellesaga and Grantham 1973; Welling et al. 1985; Lopes and Guggino 1987; Kirk et al 1987). Since cell swelling undoubtably increases membrane tension (Kelly and Macklem 1988), swollen amphibian proximal tubule cells would lose K because of an increase in the open probability of stretch-activated K channels. The additional exit of bicarbonate and water would restore the cells to their original volume.