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Potassium channel inhibition reduces cell proliferation in the GH3 pituitary cell line
Author(s) -
Vaur S.,
BressonBepoldin L.,
Dufy B.,
Tuffet S.,
DufyBarbe L.
Publication year - 1998
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/(sici)1097-4652(199812)177:3<402::aid-jcp4>3.0.co;2-z
Subject(s) - intracellular , cell growth , extracellular , channel blocker , cell culture , cell cycle , potassium channel , tetraethylammonium , microbiology and biotechnology , cell , potassium channel blocker , chemistry , second messenger system , biophysics , tetraethylammonium chloride , biology , calcium , biochemistry , potassium , genetics , organic chemistry
Potassium (K + ) conductances are known to be involved in cell proliferation of a number of nonexcitable cell types. The nature of the mechanism by which K + channel inhibition reduces cell proliferation has remained elusive despite intensive search. We investigated whether such a phenomenon could be demonstrated in excitable cells, using the GH3 pituitary cell line as a cell model. Our aims were: (1) to study the effect of K + channel inhibition on the proliferation of GH3 cells; and (2) to investigate the putative intracellular signals involved in this inhibition. Tetraethylammonium chloride (TEA), a blocker of the calcium (Ca 2+ )‐dependent K + conductances of GH3, was found to reversibly inhibit cell proliferation, as measured by 3 H‐thymidine incorporation. Cell cycle block specifically occurred at the G1/S phase of the cell cycle. This inhibition of proliferation was observed for 1–4 mM TEA, which suppressed most of the Ca 2+ ‐activated K + current and part of the inward rectifying K + current, as shown by electrophysiological experiments. Increasing extracellular K + concentrations with KCl also inhibited cell proliferation in a dose‐dependent manner. Both TEA and KCl depolarized the cells and increased intracellular Ca 2+ levels ([Ca 2+ ]i), showing that, in this type of excitable cell, inhibition of cell proliferation can be associated with elevated Ca 2+ levels. Ca 2+ and membrane resting potential (MRP) were considered as possible messengers of this inhibition. Our results suggest that cell cycle arrest of GH3 cells by K + channel block probably involves an additional pathway, distinct from those of Ca 2+ and MRP. J. Cell. Physiol. 177:402–410, 1998. © 1998 Wiley‐Liss, Inc.