Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Pflugers Arch
2003 Oct 01;4471:44-54. doi: 10.1007/s00424-003-1121-0.
Show Gene links
Show Anatomy links
Mechanisms of the inhibition of Shaker potassium channels by protons.
Starkus JG
,
Varga Z
,
Schönherr R
,
Heinemann SH
.
???displayArticle.abstract???
Potassium channels are regulated by protons in various ways and, in most cases, acidification results in potassium current reduction. To elucidate the mechanisms of proton-channel interactions we investigated N-terminally truncated Shaker potassium channels (Kv1 channels) expressed in Xenopus oocytes, varying pH at the intracellular and the extracellular face of the membrane. Intracellular acidification resulted in rapid and reversible channel block. The block was half-maximal at pH 6.48, thus even physiological excursions of intracellular pH will have an impact on K+ current. The block displayed only very weak voltage dependence and C-type inactivation and activation were not affected. Extracellular acidification (up to pH 4) did not block the channel, indicating that protons are effectively excluded from the selectivity filter. Channel current, however, was reduced greatly due to marked acceleration of C-type inactivation at low pH. In contrast, inactivation was not affected in the T449V mutant channel, in which C-type inactivation is impaired. The pH effect on inactivation of the wild-type channel had an apparent pK of 4.7, suggesting that protonation of extracellular acidic residues in Kv channels makes them subject to pH regulation.
Baukrowitz,
Two functionally distinct subsites for the binding of internal blockers to the pore of voltage-activated K+ channels.
1996, Pubmed
Baukrowitz,
Two functionally distinct subsites for the binding of internal blockers to the pore of voltage-activated K+ channels.
1996,
Pubmed
Busch,
Current inactivation involves a histidine residue in the pore of the rat lymphocyte potassium channel RGK5.
1991,
Pubmed
,
Xenbase
Claydon,
Inhibition of the K+ channel kv1.4 by acidosis: protonation of an extracellular histidine slows the recovery from N-type inactivation.
2000,
Pubmed
,
Xenbase
del Camino,
Tight steric closure at the intracellular activation gate of a voltage-gated K(+) channel.
2001,
Pubmed
Deutsch,
Modulation of K+ currents in human lymphocytes by pH.
1989,
Pubmed
Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed
Fakler,
Identification of a titratable lysine residue that determines sensitivity of kidney potassium channels (ROMK) to intracellular pH.
1996,
Pubmed
,
Xenbase
Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed
Heinemann,
Nonstationary noise analysis and application to patch clamp recordings.
1992,
Pubmed
Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase
Jäger,
Regulation of a mammalian Shaker-related potassium channel, hKv1.5, by extracellular potassium and pH.
2001,
Pubmed
Jäger,
Regulation of mammalian Shaker-related K+ channels: evidence for non-conducting closed and non-conducting inactivated states.
1998,
Pubmed
Kehl,
Molecular determinants of the inhibition of human Kv1.5 potassium currents by external protons and Zn(2+).
2002,
Pubmed
Loots,
Protein rearrangements underlying slow inactivation of the Shaker K+ channel.
1998,
Pubmed
López-Barneo,
Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.
1993,
Pubmed
,
Xenbase
Mannuzzu,
Direct physical measure of conformational rearrangement underlying potassium channel gating.
1996,
Pubmed
,
Xenbase
Melishchuk,
Mechanism underlying slow kinetics of the OFF gating current in Shaker potassium channel.
2001,
Pubmed
Pérez-Cornejo,
H+ ion modulation of C-type inactivation of Shaker K+ channels.
1999,
Pubmed
Pomès,
Molecular mechanism of H+ conduction in the single-file water chain of the gramicidin channel.
2002,
Pubmed
Steffan,
Error estimates for results of nonstationary noise analysis derived with linear least squares methods.
1997,
Pubmed
,
Xenbase
Steidl,
Differential sensitivity of voltage-gated potassium channels Kv1.5 and Kv1.2 to acidic pH and molecular identification of pH sensor.
1999,
Pubmed
,
Xenbase
