Regulation of a mammalian Shaker‐related potassium channel, hKv1.5, by extracellular potassium and pH

FEBS Letters

Grissmer, Stephan¹  Jäger, Heike¹ 

[1] Department of Applied Physiology, University of Ulm, Albert-Einstein-Allee 11, D-89081 Ulm, Germany

关键词: Shaker-related K+ channel;    Patch clamp technique;    K+ dependence;    pH dependence;   

DOI  :  10.1016/S0014-5793(00)02396-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Using the whole-cell recording mode of the patch-clamp technique we studied the effects of removal of extracellular potassium, [K⁺]_o, on a mammalian Shaker-related K⁺ channel, hKv1.5. In the absence of [K⁺]_o, current through hKv1.5 was similar to currents obtained in the presence of 4.5 mM [K⁺]_o. This observation was not expected as earlier results had suggested that either positively charged residues or the presence of a nitrogen-containing residue at the external TEA⁺ binding site (R487 in hKv1.5) caused current loss upon removal of [K⁺]_o. However, the current loss in hKv1.5 was observed when the extracellular pH, pH_o, was reduced from 7.4 to 6.0, a behavior similar to that observed previously for current through mKv1.3 with a histidine at the equivalent position (H404). These observations suggested that the charge at R487 in hKv1.5 channels was influenced by other amino acids in the vicinity. Replacement of a histidine at position 463 in hKv1.5 by glycine confirmed this hypothesis making this H463G mutant channel sensitive to removal of [K⁺]_o even at pH_o 7.4. We conclude that the protonation of H463 at pH 7.4 might induce a pK _a shift of R487 that influences the effective charge at this position leading to a not fully protonated arginine. Furthermore, we assume that the charge at position 487 in hKv1.5 can directly or indirectly disturb the occupation of a K⁺ binding site within the channel pore possibly by electrostatic interaction. This in turn might interfere with the concerted transition of K⁺ ions resulting in a loss of K⁺ conduction.

【 授权许可】

Unknown