Regulatory volume decrease in cultured astrocytes. I. Potassium- and chloride-activated permeability

Abstract

Regulatory volume decrease (RVD) in detached cerebellar astrocytes in culture after acute exposure to hyposmolarity was characterized in this and the accompanying paper [H. Pasantes-Morales, R. A. Murray, R. Sanches-Olea, and J. Moran. Am. J. Physiol. 266 (Cell Physiol. 35): C172-C178, 1994]. RVD was independent of extracellular calcium, was accelerated at pH 8-9 and retarded at pH 6, and was reduced at temperatures < 18 degrees C. The cationic pathway activated by hyposmolarity was specific for K+ and Rb+, since RVD was abolished and secondary swelling occurred when these ions replaced Na+. However, Li+, choline, tris(hydroxymethyl)aminomethane, and glucosamine, all as Cl- salts, did not affect RVD. The anion pathway was unselective, since RVD was inhibited when NaCl was replaced by anion K+ salts with a permeability rank of SCN- = I- > NO3- > Cl- > benzoate > acetate >> SO3- > gluconate. RVD was unaffected by bumetanide (50 microM) and weakly inhibited by furosemide (2 mM). Quinidine but not other K+ channel blockers inhibited RVD, and its effect was reversed by gramicidin. RVD was inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and dipyridamole but not by diphenylamine-2-carboxylate or anthracene-9-carboxylate. These results suggest that diffusion possibly via channels rather than cotransporters is involved in the swelling-activated K+ and Cl- fluxes. Gramicidin did not change astrocyte volume in isosmotic conditions, but greatly accelerated RVD, suggesting that low Cl- permeability in isosmotic conditions markedly increases by swelling, thus making K+ permeability the rate-limiting step for RVD.

Channels and Volume Changes in the Life and Death of the Cell

“…in Hoffmann et al, 2009). In other cells-such as brain cells-following hypotonic swelling, depolarization generated by the Cl -efflux occurs across the volume-regulated Cl -channel, and in these cells RVD is essentially Ca 21 -independent (Pasantes- Morales et al, 1994;Morán et al, 1997) and the K 1 regulatory fluxes permeate across voltage-gated K 1 channels. Subtypes of Kv involved in the different cell types include Kv1.3 in lymphocytes and murine spermatozoa, Kv1.4.2 and Kv1.4.3 in myocytes, and Kv1.5 in lymphocytes and spermatozoa.…”

The inhibitor of volume‐regulated anion channels DCPIB activates TREK potassium channels in cultured astrocytes

“…Pharmacological studies have suggested that astrocyte swelling can also elicit an increase in K + conductance (Pasantes-Morales et al, 1994). However, electrophysiological evidence for K + channel activated by hypotonicity is still lacking.…”

Chloride current activated by hypotonicity in cultured human astrocytoma cells

“…Indeed, astrocytes in culture swell after exposure to solutions of reduced osmolarity and then recover cell volume despite the persistence of the hyposmotic condition (Kimelberg & O'Connor, 1988;Lewis & Donaldson, 1990). It has been shown that RVD in astrocytes is inhibited by the chloride exchanger blockers 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS), 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS), niflumic acid and anthracene 9-carboxylic acid (9-AC; Kimelberg, Rose, Barron, Waniewski & Cragoe, 1989; Sanches-Olea, Pena, Moran & Pasantes-Morales, 1993;Pasantes-Morales, Murray, Lilja & Moran, 1994). Swelling of astrocytes was shown to cause changes in electrophysiological properties (Kimelberg & O'Connor, 1988;Walz & Mukerji, 1988; Kimmelberg, Anderson & Kettenmann, 1990a).…”