Swelling-activated cation-selective channels in A6 epithelia are permeable to large cations.
Effects of basolateral monovalent cation replacements (Na+ by Li+, K+, Cs+, methylammonium, and guanidinium) on permeability to 86Rb of volume-sensitive cation channels (VSCC) in the basolateral membrane and on regulatory volume decrease (RVD), elicited by a hyposmotic shock, were studied in A6 epithelia in the absence of apical Na+ uptake. A complete and quick RVD occurred only when the cells were perfused with Na+ or Li+ saline. With both cations, hypotonicity increased basolateral 86Rb release (RblRb), which reached a maximum after 15 min and declined back to control level. When the major cation was K+, Cs+, methylammonium, or guanidinium, the RVD was abolished. Methylammonium induced a biphasic time course of cell thickness (Tc), with an initial decline of Tc followed by a gradual increase. With K+, Cs+, or guanidinium, Tc increased monotonously after the rapid initial rise evoked by the hypotonic challenge. In the presence of K+, Cs+, or methylammonium, RblRb remained high during most of the hypotonic period, whereas with guanidinium blockage of RblRb was initiated after 6 min of hypotonicity, suggesting an intracellular location of the site of action. With all cations, 0.5 mM basolateral Gd3+ completely blocked RVD and fully abolished the RblRb increase induced by the hypotonic shock. The lanthanide also blocked the additional volume increase induced by Cs+, K+, guanidinium, or methylammonium. When pH was lowered from 7. 4 to 6.0, RVD and RblRb were markedly inhibited. This study demonstrates that the VSCCs in the basolateral membrane of A6 cells are permeable to K+, Rb+, Cs+, methylammonium, and guanidinium, whereas a marked inhibitory effect is exerted by Gd3+, protons, and possibly intracellular guanidinium.
Laboratory of Physiology, K. U. Leuven, Campus Gasthuisberg, B-3000 Leuven, Belgium.
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Van Driessche
D000818:Animals; D002414:Cations, Monovalent / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D002586:Cesium / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D008744:Methylamines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012414:Rubidium Radioisotopes / Q000493:pharmacokinetics; D012965:Sodium Chloride / Q000494:pharmacology
D002414:Cations, Monovalent; D007473:Ion Channels; D008744:Methylamines; D012414:Rubidium Radioisotopes; D002586:Cesium; D012965:Sodium Chloride; D008094:Lithium; C027451:methylamine; D011188:Potassium