| Autor: |
A, El Harchi, H, Zhang, J C, Hancox |
| Rok vydání: |
2010 |
| Předmět: |
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| Zdroj: |
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 61(6) |
| ISSN: |
1899-1505 |
| Popis: |
KCNQ1 is responsible for the pore-forming subunit of channels that mediate the cardiac 'IKs' potassium channel current. The S140G KCNQ1 gain-of-function mutation is responsible for a form of heritable atrial fibrillation. Here the action potential (AP) voltage clamp technique was used to elucidate the effect of S140G KCNQ1 on the profile of recombinant I(Ks) during atrial and ventricular APs applied to KCNQ1+KCNE1 expressing CHO cells, at 37°C. Under conventional voltage clamp the S140G KCNQ1 mutation shifted voltage-dependent activation by ≈-62 mV, with a marked instantaneous current component evident on membrane depolarisation. Under atrial AP clamp, cells expressing wild-type (WT) KCNQ1 exhibited modest outward currents during atrial repolarisation, whilst those expressing S140G KCNQ1 exhibited a marked instantaneous outward current and peak repolarising current4-fold that for WT KCNQ1. Under ventricular AP clamp, both WT and mutant KCNQ1 conditions showed greater peak repolarising current than when an atrial AP command was used and the S140G mutation resulted in peak repolarising current that was3-fold that for WT KCNQ1. We conclude that the S140G KCNQ1 mutation would be predicted to augment substantially repolarising current both early and throughout atrial APs and, in principle, also to influence markedly ventricular AP repolarisation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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