What is the clinical evidence from this study?

Study design: Other. Intervention: External protons (H+o) and Zn2+. Primary outcome: Reduction of maximum conductance (g(max)).

What question did this study set out to answer?

To determine the molecular mechanisms and structural determinants mediating the inhibition of human Kv1.5 potassium currents by external protons and zinc ions.

May 1, 2002The Journal of PhysiologyOpen Access

Molecular determinants of the inhibition of human Kv1.5 potassium currents by external protons and Zn2+

View Full Paper

Ask AI

Bookmark

Key result

External protons and Zn2+ inhibited human Kv1.5 potassium currents (pK(H) 6.8 at zero K+(o)) by binding to histidine residues in the pore turret to stabilize an inactivated state.

Population

Human Kv1.5 channels expressed in HEK293 cells

Design

Preclinical

Authors

SKSteven J. KehlLawrence Livermore National Laboratory CECyrus EduljeeVancouver Coastal Health DKDaniel KwanUniversity of British Columbia

Discussion

Member takes

Implication

Should not change arrhythmia management; leaves open whether proton/Zn2+ modulation of Kv1.5 contributes to human atrial electrophysiology.

Key Points

To determine the molecular mechanisms and structural determinants mediating the inhibition of human Kv1.5 potassium currents by external protons and zinc ions.
Expressed wild-type and mutated human Kv1.5 channels in HEK293 cells to record macroscopic and gating currents across various external pH levels and potassium concentrations.
Conducted site-directed mutagenesis targeting channel turret and pore residues, including H463Q, R487V, and the non-conducting mutant W472F.
External protons caused a concentration-dependent, reversible reduction in maximum conductance, with the pK_H shifting from 6.8 at 0 mM external K+ to 6.2 at 5 mM and 6.0 at 140 mM through a non-competitive interaction (K_D 0.5–1.0 mM).
Gating charge measurements in the W472F mutant showed that maximal charge (Q_max) and charge immobilization were preserved when shifting from pH 7.4 to pH 5.4.
Channel inhibition by external protons and zinc was substantially attenuated by the turret mutation H463Q or the pore-mouth mutation R487V.

Structured PICO

Population

Human Kv1.5 channels expressed in HEK293 cells

Intervention

External protons (H+o) and Zn2+ exposure, and site-directed mutagenesis (H463Q, R487V, W472F)

Outcome

Inhibition of macroscopic hKv1.5 currents (reduction of maximum conductance)surrogate

H+ or Zn2+ binding to histidine residues in the pore turret of human Kv1.5 channels stabilizes an inactivated state, reducing potassium currents.

Cite This Study

Kehl et al. (2002) studied this question. External protons (H+o) and Zn2+ was evaluated on Reduction of maximum conductance (g(max)). External protons and Zn2+ inhibited human Kv1.5 potassium currents (pK(H) 6.8 at zero K+(o)) by binding to histidine residues in the pore turret to stabilize an inactivated state.

synapsesocial.com/papers/6a9bd7cb15055755eb0260dc https://doi.org/10.1113/jphysiol.2001.014456

View Full Paper

Ask AI

Bookmark

Implication

Should not change arrhythmia management; leaves open whether proton/Zn2+ modulation of Kv1.5 contributes to human atrial electrophysiology.

Molecular determinants of the inhibition of human Kv1.5 potassium currents by external protons and Zn2+

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Molecular determinants of the inhibition of human Kv1.5 potassium currents by external protons and Zn2+

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider