Intracellular protons control the affinity of skeletal muscle ATP‐sensitive K+ channels for potassium‐channel‐openers

FEBS Letters

Depresle, Yves¹  Forestier, Cyrille¹  Vivaudou, Michel¹ 

[1] Laboratoire de Biophysique Moléculaire et Cellulaire (URA CNRS 520), Centre d'Etudes Nucléaires de Grenoble, 85X, 38041 Grenoble, France

关键词: Levcromakalim;    SR 47063;    K-ATP channel;    pH;    Rana esculenta;    K-ATP channel;    ATP-sensitive K+ channel;    KCO;    potassium channel opener;    DMSO;    dimethylsulphoxide;    SR 47063;    4-(2-cyanoimino-1;    2-dihydropyrid-1-yl)-6-nitro-2;    2-dimethyl-2H-1-benzopyran;    Levcromakalim;    (-)-6-cyano-3;    4-dihydro-2;    2-dimethyl-trans-4-(2-oxo-1-pyrrolidyl)-2H-1-benzopyran-3-ol;   

DOI  :  10.1016/0014-5793(93)81088-H

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Levcromakalim, a potential antihypertensive agent, is known to activate potassium channels dependent on intracellular ATP (K-ATP channels). In inside-out patches excised from frog skeletal muscle, levcromakalim or a related compound, SR 47063, caused a strong and persistent activation of K-ATP channels at a cytoplasmic pH of 7.1. However, at pH 6, these activators could no longer affect the K-ATP currents. Conversely, in the continuous presence of activator, lowering pH from 7.1 to 6 returned channel activity to its level in pH 6 alone. After wash-out of the activator, recovery from activation took minutes at pH 7.1 but only seconds at pH 6, thus ruling out an effect of protons on the activators in solution. These experiments suggest that K-channel-activators are unable to bind to their receptor when it is protonated, and more generally, they provide evidence at the microscopic level for proton-induced allosteric modulation of drug-receptor interaction.

【 授权许可】

Unknown