title: Volume-sensitive outwardly rectifying chloride channel in white adipocytes from normal and diabetic mice.
abstract: The volume-sensitive outwardly rectifying (VSOR) chloride channel is ubiquitously expressed and involved in cell volume regulation after osmotic swelling, called regulatory volume decrease (RVD), in various cell types. In adipocytes, the expression of the VSOR channel has not been explored to date. Here, by employing the whole-cell patch-clamp technique, we examined whether or not the VSOR channel is expressed in white adipocytes freshly isolated from epididymal fat pads of normal (C57BL/6 or KK) and diabetic (KKA(y)) mice. Whole cell voltage-clamp recordings revealed that Cl(-) currents were gradually activated upon cell swelling induced by application of a hypotonic solution, both in normal and diabetic adipocytes. Although both the mean cell size (or cell capacitance) and the current magnitude in KKA(y) adipocytes were larger than those in C57BL/6 cells, the current density was significantly lower in KKA(y) adipocytes (23.32 +/- 1.94 pA in C57BL/6 adipocytes vs. 13.04 +/- 2.41 pA in KKA(y) adipocytes at +100 mV). Similarly, the current density in diabetic KKA(y) adipocytes was lower than that in adipocytes from KK mice (a parental strain of KKA(y) mice), which do not present diabetes until an older age. The current was inhibited by Cl(-) channel blockers, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) and glibenclamide, or hypertonic solution, and showed outward rectification and inactivation kinetics at large positive potentials. These electrophysiological and pharmacological properties are consistent with those of the VSOR channel in other cell types. Moreover, adipocytes showed RVD, which was inhibited by NPPB. In KKA(y) adipocytes, RVD was significantly slower (tau; 8.42 min in C57BL/6 adipocytes vs. 11.97 min in KKA(y) adipocytes) and incomplete during the recording period (25 min). It is concluded that the VSOR channel is functionally expressed and involved in volume regulation in white adipocytes. RVD is largely impaired in adipocytes from diabetic mice, presumably as a consequence of the lower density of the functional VSOR channel in the plasma membrane.
authors.affiliation: Dept. of Physiology, Tokyo Medical Univ., 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan. hana@tokyo-med.ac.jp
authors.forename: Hana
authors.initials: H
authors.lastname: Inoue
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Okada
authors.forename: Masato
authors.initials: M
authors.lastname: Konishi
mesh_terms: D052438:Adipocytes, White / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D048429:Cell Size; D002478:Cells, Cultured; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018408:Patch-Clamp Techniques
chemical_list: D018118:Chloride Channels; D007004:Hypoglycemic Agents; D005905:Glyburide