Induction of human myeloblastic ml-1 cell g1 arrest by suppression
of k+ channel activity.
Xu, Bo, Brenda A. Wilson, and Luo Lu.
Department of Physiology and Biophysics, and Biochemistry and
Molecular Biology, Wright State University, School of Medicine,
Dayton, OH 45435
APStracts 3:0218C, 1996.
Our previous studies have shown that a voltage-gated K+ channel is
highly expressed in proliferating human myeloblastic ML-1 cells and
is suppressed in the early stages of TPA-induced ML-1 cell
differentiation. In the present study, we report that inhibition of
the K+ channel activity by 4-aminopyridine (4-AP) suppressed ML-1
cell proliferation, as measured by DNA synthesis. Cell-cycle mapping
indicated that ML-1 cells were arrested in G1 phase following 24 hour
treatment with 4-AP. Blockade of ML-1 cells at the G1/S boundary of
the cell-cycle with aphidicolin revealed that ML-1 cells past the G1
check point were capable of entering S phase and synthesizing DNA
independent of the channel blockade. ML-1 cell differentiation,
measured by CD14 marker protein expression, revealed that the effect
of 4-AP was to cause growth arrest and didn't cause differentiation.
Dephosphorylation of retinoblastoma protein (pRb) accompanied
inhibition of ML-1 cell proliferation and suggested that suppression
of K+ channel activity by 4-AP is associated with retinoblastoma
protein-mediated G1 arrest in ML-1 cells. Moreover, we found that ML
-1 cell volume increased 35 + 7% after 4-AP treatment, which could be
an early event triggering inhibition of ML-1 cell proliferation.
These findings suggest that a 4-AP sensitive K+ channel may play an
important role in the transduction of mitogenic signals in ML-1
cells.
Received 31 January 1996; accepted in final form 26 June 1996.
APS Manuscript Number C60-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996