Cell volume-sensitive sodium channels upregulated by glucocorticoids in U937 macrophages.
Glucocorticoids exert their anti-inflammatory action in part by influencing macrophages. As regulation of macrophage function involves ion channels, the present study was performed to elucidate the influence of glucocorticoids on macrophage ion channel activity. To this end, the effects of corticosteroids on the sodium conductance in human monocytic cells (U937) was studied using whole-cell and outside-out patch-clamp techniques. Increasing extracellular osmolarity from 310 to 420 mosmol/kg led to cell shrinkage followed by marked activation of inward whole-cell current from -36+/-2 to -72+/-9 pA (n=13; recorded at -150 mV voltage with CsCl intracellular solution, NaCl extracellular solution) while outward current remained unchanged. The increase of inward current was accompanied by a positive shift of reversal potential and was sensitive to amiloride (100 microM). The activation of inward current by shrinkage was not observed when external sodium was replaced by potassium, indicating that the shrinkage-stimulated conductance is sodium selective. Outside-out single-channel measurements revealed a unitary conductance of 6+/-1 pS (n=5) for the sodium-selective amiloride-sensitive current. Pretreating the cells with deoxycorticosterone (100 nM/6 h) markedly upregulated the shrinkage-activated Na+ current. In conclusion, human macrophage-like U937 cells express a sodium-selective shrinkage-activated channel which is upregulated by corticosteroids. Activation of the channel may increase cell volume, an effect of glucocorticoids in other cells.
Gamper
N
N
Department of Physiology,  University of Tuebingen, Germany.
Huber
S M
SM
Badawi
K
K
Lang
F
F
D000584:Amiloride / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects; D002586:Cesium; D002712:Chlorides; D003900:Desoxycorticosterone / Q000494:pharmacology; D004553:Electric Conductivity; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D012965:Sodium Chloride; D012996:Solutions; D020298:U937 Cells
D002712:Chlorides; D005938:Glucocorticoids; D015222:Sodium Channels; D012996:Solutions; D002586:Cesium; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D011189:Potassium Chloride; D000584:Amiloride; C028019:cesium chloride