HERG1 Currents in Native K562 Leukemic Cells Marı ´a S. Cavarra Silvana M. del Mo ´naco Yanina A. Assef Cristina Ibarra Basilio A. Kotsias Received: 18 June 2007 / Accepted: 18 June 2007 / Published online: 1 September 2007 Ó Springer Science+Business Media, LLC 2007 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, dif- ferentiation and/or apoptosis. K562 cells (a chronic myeloid leukemic human cell line) express both the full- length (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: repolari- zation to voltages negative to 40 mV produced a transient peak inward tail current, characteristic of HERG1 chan- nels. Cells were exposed to a HERG-specific channel blocker, E4031. Half-maximal inhibitory concentration (IC 50 ) of the blocker was 4.69 nM. The kinetics of the HERG1 current in K562 cells resembled the rapid com- ponent 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 consti- tutes an apoptotic signal. However, we found that K562 HERG1 whole-cell currents were not activated by H 2 O 2 . Keywords HERG1 K + channel  H 2 O 2  E4031  K562 Introduction The ether-a-go-go-related gene 1 (erg1) codes the con- ducting a-subunit of the voltage-activated K + channel ERG1 (Warmke & Ganetzky, 1994). Four a-subunits co- assemble to form the conducting core of ERG channels; each a-subunit consists of six transmembrane a-helical domains and intracellular N and C termini (Warmke & Ganetzky, 1994). The human erg1 gene (herg1), located on chromosome 7, is composed of 15 exons (Curran et al., 1995; Itoh et al., 1998) and encodes for at least four iso- forms: HERG1a, HERG1b, HERG-USO and HERG-sm. HERG1a was the first characterized isoform and is the longest one since the others have shorter N-terminal (1b) or C-terminal (USO, sm) regions (Warmke & Ganetzky, 1994; Kupershmidt et al., 1998; Lees-Miller et al., 1997; Shoeb, Malykhina & Akbarali, 2003). HERG1 was found to be abundantly expressed in the heart, where it is responsible for the rapid component of the delayed rectifier K + current (I Kr ), playing a critical role in normal cardiac repolarization (Sanguinetti et al., 1995; Curran et al., 1995; Li et al., 1996). Moreover, it has been linked to the long QT syndrome type 2 (LQT2), an inher- ited or acquired cardiac disorder (Curran et al., 1995; Sanguinetti et al., 1995). Several kinetic and pharmacological features define both expressed HERG1 and native I Kr currents. First, HERG1 M. S. Cavarra  S. M. del Mo ´naco  Y. A. Assef  B. A. Kotsias (&) Laboratorio de Neurofisiologı ´a, Instituto de Investigaciones Me ´dicas Alfredo Lanari, Universidad de Buenos Aires- CONICET, C. de Malvinas 3150, Buenos Aires 1427, Argentina e-mail: kotsias@mail.retina.ar C. Ibarra Laboratorio de Fisiopatogenia, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires 1121, Argentina 123 J Membrane Biol (2007) 219:49–61 DOI 10.1007/s00232-007-9060-x