What question did this study set out to answer?

To determine whether functional heteromeric channels can be formed by co-assembling rat SK3 potassium channel subunits with either SK1 or SK2 subunits.

January 1, 2004Journal of Biological ChemistryOpen Access

The SK3 Subunit of Small Conductance Ca2+-activated K+ Channels Interacts with Both SK1 and SK2 Subunits in a Heterologous Expression System

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Population

Heterologous expression system expressing rat SK3 (rSK3), SK1, and SK2 potassium channel subunits

Comparison

Co-expression of rSK3 with rSK2 or SK1 vs Expression of individual subunits

Design

Preclinical

Authors

AMAlan MonaghanUniversity College London DBDavid BentonSwansea University PBParmvir K. BahiaUniversity of South Florida

Discussion

Member takes

Implication

Hypothesis-generating for SK3 heteromer effects on channel pharmacology; leaves open relevance to human cardiovascular disease.

Key Points

To determine whether functional heteromeric channels can be formed by co-assembling rat SK3 potassium channel subunits with either SK1 or SK2 subunits.
Engineered pharmacological mutant subunits, including UCL 1848-insensitive rSK3VK, dominant-negative hSK1YP, and tetraethylammonium chloride (TEA)-sensitized rSK3VF.
Co-expressed combinations of SK3 with SK1 or SK2 in a heterologous expression system to evaluate channel function and pharmacology.
Used antibody-staining assays to evaluate whether subunit interactions altered protein trafficking and cell-surface expression.
Co-expression of rSK3VK with rSK2 produced functional channels with an intermediate UCL 1848 sensitivity (IC50 ~5 nM vs 120 pM for rSK2 and >300 nM for rSK3VK).
Co-transfection of rSK3VF and hSK1 resulted in TEA sensitivity identical to hSK1 alone (IC50 ~15 mM vs 0.3 mM for rSK3VF), while dominant-negative hSK1YP and rat SK1 dramatically suppressed SK3 current.
Antibody staining revealed that SK1 interaction prevents functional SK3 subunits from reaching the cell surface, reducing functional surface channel density.

Structured PICO

Population

Heterologous expression system expressing rat SK3 (rSK3), SK1, and SK2 potassium channel subunits

Intervention

Co-expression of rSK3 with rSK2 or SK1 (human or rat)

Comparator

Expression of individual subunits (e.g., rSK2 alone, rSK3VK alone, hSK1 alone)

Outcome

Formation of functional heteromeric channels and changes in protein trafficking, cell surface expression, and channel pharmacologysurrogate

SK3 subunits can form functional heteromeric channels with SK2 and interact with SK1 to alter protein trafficking and cell surface expression.

Cite This Study

Monaghan et al. (2004) studied this question.

synapsesocial.com/papers/6a70ef17ac440176ef299da8 https://doi.org/10.1074/jbc.m308070200

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The SK3 Subunit of Small Conductance Ca2+-activated K+ Channels Interacts with Both SK1 and SK2 Subunits in a Heterologous Expression System

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

The SK3 Subunit of Small Conductance Ca2+-activated K+ Channels Interacts with Both SK1 and SK2 Subunits in a Heterologous Expression System

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider