INVESTIGADORES
IBARRA cristina Adriana
artículos
Título:
HERG1 currents in native K562 leukemic cells
Autor/es:
CAVARRA MS, DEL MÓNACO SM, ASSEF YA, IBARRA C, KOTSIAS BA
Revista:
JOURNAL OF MEMBRANE BIOLOGY
Editorial:
Springer
Referencias:
Año: 2007 vol. 219 p. 49 - 61
ISSN:
0022-2631
Resumen:
Abstract
The human ether-a-go-go related gene
(HERG1) K+ channel is expressed in neoplastic cells, in
which it was proposed to play a role in proliferation, differentiation
and/or apoptosis. K562 cells (a chronic
myeloid leukemic human cell line) express both the fulllength
(herg1a) and the N-terminally truncated (herg1b)
isoforms of the gene, and this was confirmed with Western
blots and coimmunoprecipitation experiments. Whole-cell
currents were studied with a tail protocol. Seventy-eight
percent of cells showed a HERG1-like current: repolarization
to voltages negative to 40 mV produced a transient
peak inward tail current, characteristic of HERG1 channels.
Cells were exposed to a HERG-specific channel
blocker, E4031. Half-maximal inhibitory concentration
(IC50) of the blocker was 4.69 nM. The kinetics of the
HERG1 current in K562 cells resembled the rapid component
of the native cardiac delayed rectifier current,
known to be conducted by heterotetrameric HERG1
channels. Fast and slow deactivation time constants at
120 mV were 27.5 and 239.5 ms, respectively. Our results
in K562 cells suggest the assembling of heterotetrameric
channels, with some parameters being dominated by one of
the isoforms and other parameters being intermediate.
Hydrogen peroxide was shown to increase HERG1a K+
current in heterologous expression systems, which constitutes
an apoptotic signal. However, we found that K562
HERG1 whole-cell currents were not activated by H2O2.