Ca‐dependent regulation of Na⁺‐selective channels via actin cytoskeleton modification in leukemia cells

Abstract

With the use of the patch-clamp technique, physiological mechanisms of Na + channel regulation involving submembranous actin rearrangements were examined in human myeloid leukemia K562 cells. We found that the actin-severing protein gelsolin applied to cytoplasmic surface of membrane fragments at a high level of [Ca 2+ h (1 /xM) increased drastically the activity of Na-selective channels of 12 pS unitary conductance. In the experiments on intact cells, the elevation of [Ca 2+ ]i using the ionophore 4Br-A23187 also resulted in Na + channel activation. Addition of actin to the cytoplasmic surface of membrane patches reduced this activity to background level, likely due to actin polymerization. Our data imply that Cadependent modulations of the actin cytoskeleton may represent one of the general mechanisms of channel regulation and cell signalling.

Non‐hydrolyzable analog of GTP induces activity of Na+ channels via disassembly of cortical actin cytoskeleton

“…1B) approximated by linear regression corresponds to a single channel conductance value of about 11 pS and a reversal potential of about 20 mV; the estimation of relative permeability gives the value P Na /P K of about 3. These parameters are close to those obtained previously for Na þ channels which were activated by the agents disrupting actin cytoskeleton, such as cytochalasins [7,24] and gelsolin [18]. Fig.…”

“…The non-voltage-gated epithelial-like channels described in human leukemia K562 cells [7] are activated by disruption of membrane-associated actin ¢laments and inactivated by polymerizing actin [7,18,19]. The modulation of channel activity by actin cytoskeleton has been the only known mechanism of Na þ channel regulation in K562 cells.…”

Serum- and glucocorticoid-inducible kinase SGK1 regulates reorganization of actin cytoskeleton in mast cells upon degranulation

“…Indeed, different ion channels have been shown to be regulated by cytoskeleton dynamics. Thus, the activity of a Na ϩ channel in human myeloid leukemia K562 cells is extremely sensitive to the state of actin cytoskeleton (19,21,22,30,31). Depolymerization of actin results in Na ϩ channel activation whereas application of G-actin under conditions promoting its rapid polymerization abolishes Na ϩ channel activity (19,21,22).…”

“…Thus, the activity of a Na ϩ channel in human myeloid leukemia K562 cells is extremely sensitive to the state of actin cytoskeleton (19,21,22,30,31). Depolymerization of actin results in Na ϩ channel activation whereas application of G-actin under conditions promoting its rapid polymerization abolishes Na ϩ channel activity (19,21,22). Moreover, Na ϩ channel activity could be manipulated through capping of actin filaments and modulating the filament length, indicating that actin dynamics (capping-uncapping, filament growth-shrinkage) can be a powerful regulator of ion channel activity (31).…”

Regulation of Sodium Channel Activity by Capping of Actin Filaments

“…In B lymphocytes, cytochalasin modulates the response of volume-regulated chloride channels to the hyposmotic gradient (Levitan et al, 1995). Moreover, ion channel activity can be affected by both DNase I and gelsolin, which destabilize actin filaments (Terzic and Kurachi, 1996;Maximov et al, 1997;Lader et al, 1999). Accordingly, phalloidin, which stabilizes actin filaments, may reverse the effect of actin cytoskeleton disrupters (Terzic and Kurachi, 1996;Lader et al, 1999).…”