| 1. |
- Evans, M, et al.
(författare)
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Acetaminophen, aspirin and progression of advanced chronic kidney disease
- 2009
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 24:6, s. 1908-1918
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Klement, G., et al.
(författare)
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A tyrosine substitution in the cavity wall of a K channel induces an inverted inactivation
- 2008
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 94:8, s. 3014-3022
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Tidskriftsartikel (refereegranskat)abstract
- Ion permeation and gating kinetics of voltage-gated K channels critically depend on the amino-acid composition of the cavity wall. Residue 470 in the Shaker K channel is an isoleucine, making the cavity volume in a closed channel insufficiently large for a hydrated K+ ion. In the cardiac human ether-a-go-go-related gene channel, which exhibits slow activation and fast inactivation, the corresponding residue is tyrosine. To explore the role of a tyrosine at this position in the Shaker channel, we studied I470Y. The activation became slower, and the inactivation faster and more complex. At +60 mV the channel inactivated with two distinct rates (t1 = 20 ms, t2 = 400 ms). Experiments with tetraethylammonium and high K + concentrations suggest that the slower component was of the P/C-type. In addition, an inactivation component with inverted voltage dependence was introduced. A step to -40 mV inactivates the channel with a time constant of 500 ms. Negative voltage steps do not cause the channel to recover from this inactivated state (t » 10 min), whereas positive voltage steps quickly do (t = 2 ms at +60 mV). The experimental findings can be explained by a simple branched kinetic model with two inactivation pathways from the open state. © 2008 by the Biophysical Society.
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