What question did this study set out to answer?

To elucidate the mechanism of muscarinic K+ channel activation by G protein beta gamma subunits and contrast this pathway with the regulation of ATP-sensitive K+ channels in cardiac membranes.

June 1, 1992The Journal of General PhysiologyOpen Access

On the mechanism of G protein beta gamma subunit activation of the muscarinic K+ channel in guinea pig atrial cell membrane. Comparison with the ATP-sensitive K+ channel.

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To elucidate the mechanism of muscarinic K+ channel activation by G protein beta gamma subunits and contrast this pathway with the regulation of ATP-sensitive K+ channels in cardiac membranes.
Conducted inside-out patch clamp electrophysiology on isolated guinea pig atrial and ventricular cell membranes.
Applied purified bovine brain G beta gamma and GTP-gamma S-bound G alpha subunits under conditions testing detergent effects, heat denaturation, and GDP analogue incubations.
Purified G beta gamma directly activated atrial muscarinic K+ channels in 98.5% of patches (132 of 134) with half-maximal activation at approximately 6 nM, independent of detergent or contaminating G alpha proteins.
G i alpha subunits weakly activated muscarinic K+ channels in only 32.2% of patches (40 of 124) with roughly 20% maximal efficacy, but effectively stimulated phosphorylated ATP-sensitive K+ channels in both ventricular and atrial membranes.

Structured PICO

Population

Guinea pig atrial and ventricular cell membranes (studied using inside-out patch clamp technique)

Intervention

Application of G protein beta gamma subunit (G beta gamma) and GTP-gamma S-bound alpha subunits (G alpha *'s) of pertussis toxin (PT)-sensitive G proteins purified from bovine brain

Comparator

Detergent (CHAPS), boiled G beta gamma preparation, and G beta gamma preincubated with excessive GDP-bound G o alpha

Outcome

Activation of the muscarinic K+ channel (KACh) and ATP-sensitive K+ channel (KATP)surrogate

This preclinical study demonstrates two distinct regulatory systems of cardiac K+ channels by PT-sensitive G proteins: G i alpha activation of the KATP channel and G beta gamma activation of the KACh channel.

Discussion

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Implication

Does not alter arrhythmia management; leaves open validation of G-protein subunit selectivity in intact or diseased hearts.

Cite This Study

Ito et al. (1992) studied this question.

synapsesocial.com/papers/6a715589f44fa9f079df21d8 https://doi.org/10.1085/jgp.99.6.961

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On the mechanism of G protein beta gamma subunit activation of the muscarinic K+ channel in guinea pig atrial cell membrane. Comparison with the ATP-sensitive K+ channel.

Key Points

Structured PICO

Discussion

Implication

Cite This Study

On the mechanism of G protein beta gamma subunit activation of the muscarinic K+ channel in guinea pig atrial cell membrane. Comparison with the ATP-sensitive K+ channel.

Key Points

Structured PICO

Discussion

Implication

Cite This Study

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Also Consider