Ion Channels Involved in Cell Volume Regulation: Effects on Migration, Proliferation, and Programmed Cell Death in Non Adherent EAT Cells and Adherent ELA Cells

Abstract

This mini review outlines studies of cell volume regulation in two closely related mammalian cell lines: nonadherent Ehrlich ascites tumour cells (EATC) and adherent Ehrlich Lettre ascites (ELA) cells. Focus is on the regulatory volume decrease (RVD) that occurs after cell swelling, the volume regulatory ion channels involved, and the mechanisms (cellular signalling pathways) that regulate these channels. Finally, I shall also briefly review current investigations in these two cell lines that focuses on how changes in cell volume can regulate cell functions such as cell migration, proliferation, and programmed cell death.

CFTR Involvement in Cell Migration and Epithelial Restitution

“…Furthermore, enhanced expression of both α 6 β 4 integrin and TRPV1 receptors at the leading edge of keratinocytes after wounding has also been linked to increases in intracellular [Ca 2+ ]. Evidence appears to support a model where TRPV1-mediated increases in intracellular [Ca 2+ ] trigger the activation of transcription factors such as nuclear factor of activated T cells (NFAT) and cAMP response element binding protein (CREB) to stimulate expression of β 4 integrins in cells at the margin of the wound leading to an increase in directional migration [9]. Direct coupling between the β 1 integrin and K Ca 3.1 channel expression has been demonstrated in alveolar type II cells grown on a fibronectin matrix and inhibition of channel activity was shown to decrease the rate of migration [10].…”

“…The role of ion channels and membrane transporters in cell migration has been the subject of several recent reviews [1][2][3][4], so only a few examples will be highlighted in this section to provide the reader with an appreciation of their importance in cell motility. Ion channels and other membrane transport pathways participate in multiple housekeeping functions within cells that include regulation of membrane potential, intracellular [Ca 2+ ], cytoskeletal assembly, integrinmediated signaling, cell volume regulation, as well as the maintenance of intracellular and extracellular pH.…”

SPAK and OSR1 Sensitive Kir2.1 K⁺ Channels

“…Cellular accumulation of KCl with osmotically obliged water is followed by cell swelling [80][81][82]. Activation of Kir2.1 channels may result in blunting of cellular KCl uptake and cell swelling.…”

Upregulation of Na+,Cl--Coupled Betaine/ γ-Amino-Butyric Acid Transporter BGT1 by Tau Tubulin Kinase 2

“…Osmolyte transporters counteract cell shrinkage, which is known to parallel and facilitate suicidal cell death [51,52,53,54,55,56,57,58,59,60]. BGT1 participates in the cellular accumulation of organic osmolytes [9,10], which are well known to foster cell survival [8,26].…”