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Inward rectification in KATP channels: a pH switch in the pore.
T Baukrowitz1, S J Tucker, U Schulte
1Department of Physiology II, Ob dem Himmelreich 7, 72074 Tübingen. thomas.baukrowitz@uni-tuebingen.de
The EMBO Journal
|February 18, 1999
Summary
Inward-rectifier potassium channels (Kir channels) show pH-dependent rectification. KATP channel block by polyamines weakens at acidic pH, impacting cellular excitation and pH links.
Area of Science:
- Physiology
- Molecular Biology
- Biophysics
Background:
- Inward-rectifying potassium (Kir) channels stabilize cell membrane potential via polyamine block.
- Kir channel rectification is typically strong or weak, independent of physiological conditions.
- KATP channels, crucial in cardiac cells, are formed by Kir6.2 and SUR subunits.
Purpose of the Study:
- To investigate the influence of intracellular pH on polyamine-mediated rectification in KATP channels.
- To determine the structural basis and molecular mechanism of pH-dependent rectification.
Main Methods:
- Electrophysiological recordings of cardiac and cloned KATP channels (Kir6.2 + SUR).
- Systematic mutagenesis of the Kir6.2 subunit, focusing on C-terminal residues.
- Analysis of polyamine block under varying intracellular pH conditions.
Main Results:
- KATP channel rectification strength varies with intracellular pH, being prominent at basic pH and weak at acidic pH.
- This pH-dependence is specific to KATP channels compared to other Kir channel types.
- A titratable histidine residue (H216) in Kir6.2 was identified as the key structural determinant.
- Electrostatic interactions between H216 and polyamines mediate the pH-dependent block.
Conclusions:
- Polyamines' block of KATP channels is dynamically regulated by intracellular pH.
- This pH-dependent rectification provides a novel mechanism linking cellular excitation to intracellular pH.
- The findings reveal a new layer of regulation for KATP channel function in physiological contexts.