Modulation of HERG potassium channel properties by external pH.
We expressed the human eag-related gene (HERG), known to encode for the cardiac potassium channel IKr, in Chinese hamster ovary (CHO) cells. This study investigated effects of external pH (pHo) on HERG current properties using the whole-cell patch-clamp technique. We observed that current amplitude was decreased and kinetics of activation and deactivation were faster when pHo was lowered from 7. 4 to 6.0, while activation was accelerated and V1/2 negatively shifted when pHo was changed from 7.4 to 8.0. These effects can be explained by surface charge screening, amino acid group titration and/or changes in ionic atmosphere. We conclude that alterations of HERG channel by pHo could have consequences for the onset of arrhythmias during cardiac ischemia.
Quebec Heart Institute, Laval Hospital, Research Center, 2725 Chemin Ste-Foy, Ste-Foy, QC, Canada, G1V 4G5.
J
J
Bérubé
M
M
Chahine
P
P
Daleau
D000818:Animals; D016466:CHO Cells; D027682:Cation Transport Proteins; D006224:Cricetinae; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D004553:Electric Conductivity; D051638:Ether-A-Go-Go Potassium Channels; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014162:Transfection
D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG