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Effect of specific ion channel blockers on cultured schwann cell proliferation
Author(s) -
Pappas Christopher A.,
Ritchie J.M.
Publication year - 1998
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(199802)22:2<113::aid-glia2>3.0.co;2-8
Subject(s) - dids , channel blocker , charybdotoxin , tetraethylammonium , potassium channel blocker , iberiotoxin , biology , potassium channel , ion channel , inward rectifier potassium ion channel , microbiology and biotechnology , cell growth , biophysics , medicine , chemistry , biochemistry , receptor , potassium , organic chemistry , membrane , calcium
Mitogenesis in a variety of tissues is known to be inhibited by K + channel blockers such as tetraethylammonium (TEA) and 4‐aminopyridine (4‐AP). Using radiolabeled thymidine as a proliferation index we have examined what role, if any, specific K + channels have in cultured Schwann cells that have been induced to proliferate by pre‐exposure to mitogens. TEA and 4‐AP are “broad‐spectrum” in that they block a variety of different types of K + channel. In contrast, we found that α‐dendrotoxin (α‐DTX), a specific blocker of the type 1 fast delayed rectifier current (the largest component of Schwann cell K + current) does not affect proliferation, suggesting that type 1 current may not be involved in mitogenesis. This suggestion is supported by our finding that the values of the K D for the mitogenic effect (722 nM, 4‐AP; 13 mM, TEA) are much larger than the corresponding electrophysiological values for type 1 channels (0.1 mM, 4‐AP; 0.2 mM, TEA). Charybdotoxin (200 nM) and iberiotoxin (100 nM), inhibitors of Ca 2+ ‐activated K + channels, cesium (5 mM), an inhibitor of inward rectifier channels, and furosemide (100 μM), which blocks Na + /K + /Cl − cotransport, all had no effect on proliferation. Interestingly, 4,4′‐diisothiocyanatostilbene 2,2′‐disulphonate (DIDS), which blocks voltage‐gated Cl − channels, reduced proliferation. In summary, broad‐spectrum K + channel blockers inhibit Schwann cell proliferation, but inhibitors specific for type 1, Ca 2+ ‐activated, and inward rectifier K + channels do not. Whether the inhibition is mediated by type 2 K + channels, by an as yet unidentified Schwann cell K + channel, or by another mechanism remains unclear. GLIA 22:113–120, 1998. © 1998 Wiley‐Liss, Inc.