Mitogenesis in a variety of tissues is known to be inhibited by K+ cha
nnel blockers such as tetraethylammonium (TEA) and 4-aminopyridine (4-
AP). Using radiolabeled thymidine as a proliferation index we have exa
mined what role, if any, specific K+ channels have in cultured Schwann
cells that have been induced to proliferate by pre-exposure to mitoge
ns. TEA and 4-AP are 'broad-spectrum'' in that they block a variety of
different types of K+ channel. In contrast, we found that alpha-dendr
otoxin (alpha-DTX), a specific blocker of the type 1 fast delayed rect
ifier current (the largest component of Schwann cell K+ current) does
not affect proliferation, suggesting that type 1 current may not be in
volved in mitogenesis. This suggestion is supported by our finding tha
t the values of the K-D for the mitogenic effect (722 nM, 4-AP; 13 mM,
TEA) are much larger than the corresponding electrophysiological valu
es for type 1 channels (0.1 mM, 4-AP; 0.2 mM, TEA). Charybdotoxin (200
nM) and iberiotoxin (100 nM), inhibitors of Ca2+-activated K+ channel
s, cesium (5 mM), an inhibitor of inward rectifier channels, and furos
emide (100 mu M), which blocks Na+/K+/Cl- cotransport, all had no effe
ct 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, Ca2+-
activated, and inward rectifier K+ channels do not. Whether the inhibi
tion is mediated by type 2 K+ channels, by an as yet unidentified Schw
ann cell K+ channel, or by another mechanism remains unclear. (C) 1998
Wiley-Liss, Inc.