Migration of transformed renal epithelial cells is regulated by K + channel modulation of actin cytoskeleton and cell volume

Abstract

Migration of transformed renal epithelial (MDCK-F) cells depends on the polarized activity of a Ca2+-sensitive K+ channel (IK channel; Pflügers Arch 432:R87-R93, 1996). This study was aimed at elucidating the functional link between the IK channel and the actin cytoskeleton which is required for cell locomotion. We monitored migration of MDCK-F cells with video microscopy, quantified filamentous actin with phalloidin binding, and measured the intracellular Ca2+ concentration ([Ca2+]i) with the fluorescent dye fura-2/AM. We compared the effects of IK channel activation or inhibition with those 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 cytochalasin D. Inhibition of migration is accompanied either by actin depolymerization (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 correlated 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 cell volume and anisotonicity elicit virtually identical effects on migration, actin filaments and [Ca2+]i. We therefore suggest that cell volume - possibly via [Ca2+]i - is the link between IK channel activity, actin filaments and migration. We propose a model for how temporal and local changes of cell volume can support the migration of MDCK-F cells.

The Ca2+-Activated K+ChannelKCNN4/KCa3.1 Contributes to Microglia Activation and Nitric Oxide-Dependent Neurodegeneration

“…KCa3.1 is involved in microglia functions (Khanna et al, 2001; present study), lymphocyte activation (for review, see Jensen et al, 2002;Schlichter and Khanna, 2002), volume regulation in red blood cells and lymphocytes (Brugnara et al, 1996;Khanna et al, 1999), and migration of renal epithelial cells and mast cells (Schwab et al, 1999;Cruse et al, 2006). Because SK channels are not voltage gated, they are well designed to contribute to the resting potential of non-excitable cells, including immune cells (e.g., microglia).…”

Involvement of regulatory volume decrease in the migration of nasopharyngeal carcinoma cells

“…Cell volume regulation depends on an intact actin cytoskeleton [19], and perturbations of cell volume themselves change the polymerisation of actin filaments. Cell swelling is accompanied by a disintegration of actin filaments, and cell shrinkage is followed by an assembly of actin filaments [20,21]. Cell migration -a process in which a complex and co-ordinated turnover of actin filaments is of central importance [2,22,23] -also relies on cell volume homeostasis.…”

Migration-associated secretion of melanoma inhibitory activity at the cell rear is supported by KCa3.1 potassium channels

“…In previous studies, it was described that the KCa3.1 channel is highly expressed in malignant melanoma cells [19]. Ion fluctuations mediated by the KCa3.1 channel are known to play a fundamental role in cell migration [23,[64][65][66], since inhibition with specific blockers or activation of this ion channel results in impaired cell mobility [23,67]. Interestingly, it was also reported that the KCa3.1 channels are only active at the rear cell pole of migrating cells due to the intracellular Ca 2+ gradient [22].…”