A. Schwab et al., Migration of transformed renal epithelial cells is regulated by K+ channelmodulation of actin cytoskeleton and cell volume, PFLUG ARCH, 438(3), 1999, pp. 330-337
Migration of transformed renal epithelial (MDCK-F) cells depends on the pol
arized activity of a Ca2+-sensitive K+ channel (IK channel; Pflugers Arch 4
32:R87-R93, 1996). This study was aimed at elucidating the functional link
between the IK channel and the actin cytoskeleton which is required for cel
l locomotion. We monitored migration of MDCK-F cells with video microscopy,
quantified filamentous actin with phalloidin binding, and measured the int
racellular Ca2+ concentration ([Ca2+](i)) with the fluorescent dye fura-2/A
M. We compared the effects of IK channel activation or inhibition with thos
e of hypotonic swelling or hypertonic shrinkage. IK channel inhibition with
charybdotoxin (CTX) or cell swelling (omission of up to 50 mmol/l NaCl) as
well as IK channel activation with 1-ethyl-2-benzimidazolinone (1-EBIO) or
cell shrinkage (addition of up to 100 mmol/l mannitol) reduce the rate of
migration dose-dependently by up to 80%, i.e., to the same extent as cytoch
alasin D. Inhibition of migration is accompanied either by actin depolymeri
zation (CTX and cell swelling) or by actin polymerization (1-EBIO and cell
shrinkage). Changes of migration and phalloidin binding induced by CTX and
cell swelling or by 1-EBIO and cell shrinkage, respectively, are linearly c
orrelated with each other. CTX and cell swelling elicit a rise of [Ca2+](i)
whereas 1-EBIO and cell shrinkage induce a slight decrease of [Ca2+](i) in
most MDCK-F cells. Taken together IK-channel-dependent perturbations of ce
ll volume and anisotonicity elicit virtually identical effects on migration
, actin filaments and [Ca2+](i). We therefore suggest that cell volume - po
ssibly via [Ca2+](i) - is the link between IK channel activity, actin filam
ents and migration. We propose a model for how temporal and local changes o
f cell volume can support the migration of MDCK-F cells.