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Cl − channel blockers inhibit transition of quiescent (G 0 ) fibroblasts into the cell cycle
Author(s) -
Zheng YaJuan,
Furukawa Tetsushi,
Tajimi Kimitaka,
Inagaki Nobuya
Publication year - 2003
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10218
Subject(s) - dids , channel blocker , chemistry , efflux , cell cycle , membrane permeability , cell cycle progression , biophysics , medicine , cell , endocrinology , biochemistry , biology , membrane , organic chemistry , calcium
Modulation of ion permeability during the cell cycle is one of the key events in cell cycle progression. We have compared the effects of K + and Cl − channel blockers on the cell cycle in synchronous and asynchronous NIH3T3 cells. The Cl − channel blocker 5‐ N ‐2‐(3‐phenylpropylamino) benzoic acid (NPPB; 0.2 mM) inhibited entry into S phase in synchronous cells but not in asynchronous cells, while the K + channel blocker 4‐aminopyridine (4‐AP) showed similar inhibitory effects in both conditions. In NIH3T3 cells synchronized by serum deprivation/replenishment, G 0 ‐to‐G 1 transition occurred within 8 h after serum addition, and the G 1 /S checkpoint at 10–14 h. NPPB applied only at 0–8 or 8–14 h after serum addition inhibited entry into S phase. Cl − permeability measured as 125 I efflux increased at 4 and 10 h after serum addition. Ki‐67‐negative cells, which represent quiescent G 0 phase cells, progressively decreased in number until 8 h after serum addition. The Cl − channel blockers (NPPB and 4,4′‐diisothiocyanatostilbene‐2,2′‐disulfonic acid [DIDS]) but not the K + channel blocker (4‐AP) significantly decreased the rate of reduction in number of Ki‐67‐negative cells. These data indicate that an increase in Cl − permeability plays an important role in reentry of quiescent cells into the proliferating phase, in addition to the known effects on passage through the G 1 /S checkpoint. © 2003 Wiley‐Liss, Inc.