Hypotonicity activates a lanthanide-sensitive pathway for K⁺ release in A6 epithelia

<jats:p> The nature of the pathway for K<jats:sup>+</jats:sup> release activated during regulatory volume decrease (RVD) in A6 epithelia was investigated by measuring cell thickness (T<jats:sub>c</jats:sub>) as an index of cell volume and by probing K<jats:sup>+</jats:sup> efflux with<jats:sup>86</jats:sup>Rb as tracer for K<jats:sup>+</jats:sup>(R<jats:sub>Rb</jats:sub>). Cell swelling was induced by sudden reduction of basolateral osmolality (from 260 to 140 mosmol/kgH<jats:sub>2</jats:sub>O). Experiments were performed in the absence of Na<jats:sup>+</jats:sup>transport. Apical R<jats:sub>Rb</jats:sub> was negligible in iso- and hyposmotic conditions. On the other hand, osmotic shock increased basolateral R<jats:sub>Rb</jats:sub>([Formula: see text]) rapidly, reaching a maximum 7 min after the peak in T<jats:sub>c</jats:sub>. Quinine (0.5 mM) completely inhibited RVD and [Formula: see text]. Also verapamil (0.2 mM) impeded volume recovery considerably; lidocaine (0.2 mM) did not exert a noticeable effect. The K<jats:sup>+</jats:sup> channel blocker Ba<jats:sup>2+</jats:sup> (30 mM) delayed RVD but could not prevent complete volume recovery. Cs<jats:sup>+</jats:sup> inhibited RVD noticeably at concentrations <40 mM. With large Cs<jats:sup>+</jats:sup> concentrations (>40 mM), the initial osmometric swelling was followed by a gradual increase of T<jats:sub>c</jats:sub>, suggesting activation of Cs<jats:sup>+</jats:sup> influx. Chronic exposure of the basolateral surface to 0.5 mM La<jats:sup>3+</jats:sup> or Gd<jats:sup>3+</jats:sup> completely abolished RVD and[Formula: see text]. Acute administration of lanthanides at the time of osmolality decrease did not affect the initial phase of RVD and reduced [Formula: see text]only slightly. Apical Gd<jats:sup>3+</jats:sup> exerted an inhibitory effect on RVD and [Formula: see text]. The effect of Gd<jats:sup>3+</jats:sup> should therefore be localized at an intracellular site. The role of Ca<jats:sup>2+</jats:sup> entry could be excluded by failure of extracellular Ca<jats:sup>2+</jats:sup>removal to inhibit volume recovery. In contrast to lanthanides, chronically and acutely administered Mg<jats:sup>2+</jats:sup> (0.5 mM) inhibited RVD and[Formula: see text] by ∼50%. These data suggest that K<jats:sup>+</jats:sup> excretion during RVD occurs through a rather poorly selective pathway that does not seem to be directly activated by membrane stretch. </jats:p>