What question did this study set out to answer?

To determine whether the G protein alpha i-3 subunit directly activates cardiac potassium channels and possesses intrinsic Gk activity.

January 1, 1989Journal of Biological ChemistryOpen Access

Recombinant αi-3 Subunit of G Protein Activates Gk-gated K+ Channels

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Population

Inside-out atrial membrane patches from guinea pigs, neonatal rats, and embryonic chick, and cyc- adenylyl…

Comparison

Recombinant alpha i-3 subunit activated by GTP… vs Recombinant alpha s subunit activated by GTP…

Design

Preclinical

Authors

RMRafael MatteraNational Institutes of Health AYAtsuko YataniElectrophysiology GKGlenn E. KirschElectrophysiology

Discussion

Member takes

Implication

Preclinical data warrant no arrhythmia management changes; extends G-protein signaling knowledge but leaves open in vivo and human relevance.

Key Points

To determine whether the G protein alpha i-3 subunit directly activates cardiac potassium channels and possesses intrinsic Gk activity.
Expressed cDNAs for G alpha i-3 and two G alpha s splice variants as recombinant fusion proteins in Escherichia coli using a T7 promoter expression system.
Assayed soluble recombinant subunits for potassium channel stimulation in inside-out atrial membrane patches from guinea pigs, neonatal rats, and embryonic chicks, as well as for cyc- adenylyl cyclase reconstitution.
Recombinant alpha i-3 activated by GTPgammaS or AlF4- stimulated single-channel potassium currents in a concentration-dependent manner across all three species, whereas recombinant alpha s showed no channel stimulation.
Stimulation of potassium channels by recombinant alpha i-3 required 30- to 50-fold higher concentrations than native human erythrocyte Gk, yielding single-channel currents indistinguishable from those evoked by acetylcholine.
Both recombinant alpha s variants reconstituted GTPgammaS-stimulated adenylyl cyclase activity at concentrations 50- to 100-fold higher than native Gs.

Structured PICO

Population

Inside-out atrial membrane patches from guinea pigs, neonatal rats, and embryonic chick, and cyc- adenylyl cyclase

Intervention

Recombinant alpha i-3 subunit (r alpha i-3) activated by GTP gamma S or AlF-4

Comparator

Recombinant alpha s subunit (r alpha s) activated by GTP gamma S, and native Gk/Gs

Outcome

Stimulation of single channel K+ currents and reconstitution of cyc- adenylyl cyclase activitysurrogate

Bacterial expression of G alpha subunits demonstrates unequivocally that Gi-3 has intrinsic Gk activity, stimulating K+ channels similarly to the natural effector acetylcholine.

Cite This Study

Mattera et al. (1989) studied this question.

synapsesocial.com/papers/6a76cb4733def31403adfd59 https://doi.org/10.1016/s0021-9258(17)31281-4

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Implication

Preclinical data warrant no arrhythmia management changes; extends G-protein signaling knowledge but leaves open in vivo and human relevance.

Recombinant αi-3 Subunit of G Protein Activates Gk-gated K+ Channels

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Recombinant αi-3 Subunit of G Protein Activates Gk-gated K+ Channels

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider