Ca-dependent regulation of Na+-selective channels via actin cytoskeleton modification in leukemia cells.
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 [Ca2+]i (1 microM) increased drastically the activity of Na-selective channels of 12 pS unitary conductance. In the experiments on intact cells, the elevation of [Ca2+]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 Ca-dependent modulations of the actin cytoskeleton may represent one of the general mechanisms of channel regulation and cell signalling.
Maximov
A V
AV
Institute of Cytology, Russian Academy of Sciences, St.-Petersburg, Russian Federation.
Vedernikova
E A
EA
Hinssen
H
H
Khaitlina
S Y
SY
Negulyaev
Y A
YA
D000199:Actins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D003599:Cytoskeleton / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology*; D004553:Electric Conductivity; D018260:Gelsolin / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000199:Actins; D018260:Gelsolin; D015222:Sodium Channels; D000001:Calcimycin; D002118:Calcium