TY - JOUR
T1 - Frequency-dependent modulation of KCNQ1 and HERG1 potassium channels.
AU - Diness, Thomas Goldin
AU - Hansen, Rie Schultz
AU - Olesen, Søren-Peter
AU - Grunnet, Morten
N1 - Keywords: Action Potentials; Animals; Cells, Cultured; Ether-A-Go-Go Potassium Channels; Female; Guinea Pigs; Humans; Ion Channel Gating; KCNQ1 Potassium Channel; Myocytes, Cardiac; Oocytes; Patch-Clamp Techniques; Potassium Channels, Voltage-Gated; Xenopus laevis
PY - 2006
Y1 - 2006
N2 - To obtain information about a possible frequency-dependent modulation of HERG1 and hKCNQ1 channels, we performed heterologous expression in Xenopus laevis oocytes. Channel activation was obtained by voltage protocols roughly imitating cardiac action potentials at frequencies of 1, 3, 5.8, and 8.3Hz. The activity of HERG1 channels was inhibited down to 65% at high frequencies. In contrast, hKCNQ1 channel activity was increased up to 525% at high frequencies. The general frequency-dependent modulation of the channels was unaffected by both co-expression of hKCNQ1 and HERG1 channels, and by the presence of the beta-subunits KCNE1 and KCNE2. In addition, the functional role of HERG1 in native guinea pig cardiac myocytes was demonstrated at different pacing frequencies by application of 10microM of the new HERG1 activator, NS1643. In conclusion, we have demonstrated that HERG1 and hKCNQ1 channels are inversely modulated by stimulation frequency.
AB - To obtain information about a possible frequency-dependent modulation of HERG1 and hKCNQ1 channels, we performed heterologous expression in Xenopus laevis oocytes. Channel activation was obtained by voltage protocols roughly imitating cardiac action potentials at frequencies of 1, 3, 5.8, and 8.3Hz. The activity of HERG1 channels was inhibited down to 65% at high frequencies. In contrast, hKCNQ1 channel activity was increased up to 525% at high frequencies. The general frequency-dependent modulation of the channels was unaffected by both co-expression of hKCNQ1 and HERG1 channels, and by the presence of the beta-subunits KCNE1 and KCNE2. In addition, the functional role of HERG1 in native guinea pig cardiac myocytes was demonstrated at different pacing frequencies by application of 10microM of the new HERG1 activator, NS1643. In conclusion, we have demonstrated that HERG1 and hKCNQ1 channels are inversely modulated by stimulation frequency.
U2 - 10.1016/j.bbrc.2006.03.072
DO - 10.1016/j.bbrc.2006.03.072
M3 - Journal article
C2 - 16581021
SN - 0006-291X
VL - 343
SP - 1224
EP - 1233
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -