Single channel kinetic analysis of the cAMP effect on IKs mutants, S209F and S27D/S92D
| Autor: | Emely Thompson, Jodene Eldstrom, David Fedida |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Potassium Channels Mutant Kinetic analysis Biophysics Stimulation KCNQ1 S27D/S92D Gating IKs Biochemistry 03 medical and health sciences Mice cAMP Cyclic AMP Animals Phosphorylation Cells Cultured Chemistry Channel kinetics Cardiac action potential Kinetics 030104 developmental biology KCNQ1 S209F Mutation KCNE1 Communication channel Research Paper |
| Zdroj: | Channels |
| ISSN: | 1933-6969 1933-6950 |
| Popis: | The IKs current is important in the heart’s response to sympathetic stimulation. β-adrenergic stimulation increases the amount of IKs and creates a repolarization reserve that shortens the cardiac action potential duration. We have recently shown that 8-CPT-cAMP, a membrane-permeable cAMP analog, changes the channel kinetics and causes it to open more quickly and more often, as well as to higher subconductance levels, which produces an increase in the IKs current. The mechanism proposed to underlie these kinetic changes is increased activation of the voltage sensors. The present study extends our previous work and shows detailed subconductance analysis of the effects of 8-CPT-cAMP on an enhanced gating mutant (S209F) and on a double pseudo-phosphorylated IKs channel (S27D/S92D). 8-CPT-cAMP still produced kinetic changes in S209F + KCNE1, further enhancing gating, while S27D/S92D + KCNE1 showed no significant response to 8-CPT-cAMP, suggesting that these last two mutations fully recapitulate the effect of channel phosphorylation by cAMP. |
| Databáze: | OpenAIRE |
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