What is the clinical evidence from this study?

Study design: Review. Population: Cardiac automaticity disorders. Intervention: RGS proteins (RGS4, RGS6) modulation.

What question did this study set out to answer?

To review the mechanisms by which regulator of G protein signaling (RGS) proteins, especially RGS6 and RGS4, control parasympathetic regulation of cardiac pacing and electrophysiology.

January 1, 2012Frontiers in PhysiologyOpen Access

RGS proteins in heart: brakes on the vagus

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Key result

RGS proteins, particularly RGS4 and RGS6, act as critical negative regulators of muscarinic M2 receptor signaling in the heart, serving as brakes on vagal stimulation.

Population

Preclinical models (mice expressing RGS-insensitive Gα mutant, mice lacking RGS6 or RGS4) and general review…

Design

Review

Authors

ASAdele StewartUniversity of Iowa

Discussion

Member takes

Implication

May guide RGS-targeted therapies for autonomic imbalance; leaves open clinical translation and safety.

Key Points

To review the mechanisms by which regulator of G protein signaling (RGS) proteins, especially RGS6 and RGS4, control parasympathetic regulation of cardiac pacing and electrophysiology.
Synthesized findings from transgenic mouse models lacking RGS6 or RGS4, or expressing an RGS-insensitive Gα(i2) mutant (G184S).
Evaluated electrophysiological endpoints including sinoatrial node action potential firing and acetylcholine-induced GIRK current (IKAch) kinetics.
Genetic deletion of RGS6 or RGS4 resulted in exacerbated carbachol-induced bradycardia and pronounced inhibition of sinoatrial node action potential firing.
Loss of RGS6 eliminated the rapid activation, deactivation kinetics, and current desensitization of acetylcholine-activated GIRK currents in pacemaker tissue.
RGS6 up-regulation was identified in cardiotoxic states such as doxorubicin exposure, pointing to its involvement in chemotherapy-induced atrial arrhythmias.

Structured PICO

Population

Preclinical models (mice expressing RGS-insensitive Gα(i2) mutant, mice lacking RGS6 or RGS4) and general review of RGS proteins in the heart

RGS proteins, especially RGS6, are critical regulators of parasympathetic signaling in the heart and represent potential therapeutic targets for diseases involving abnormal autonomic control.

Limitations

Potential for functional redundancy and compensatory changes in RGS protein expression resulting from loss of a single protein.
Lack of specific antibodies with corresponding genetic knockout controls makes detection of endogenous RGS proteins difficult in vivo.
In vivo significance of some effects observed in heterologous expression systems or isolated cells remains unclear.
Need for double knockout mice to investigate redundant, additive, or synergistic functions of RGS4 and RGS6.

Cite This Study

Adele Stewart (2012) conducted a review in Cardiac automaticity disorders. RGS proteins (RGS4, RGS6) modulation was evaluated. RGS proteins, particularly RGS4 and RGS6, act as critical negative regulators of muscarinic M2 receptor signaling in the heart, serving as brakes on vagal stimulation.

synapsesocial.com/papers/6a153f69a2f71238514e3a90 https://doi.org/10.3389/fphys.2012.00095

View Full Paper

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January 1, 2012Frontiers in PhysiologyOpen Access

RGS proteins in heart: brakes on the vagus

View Full Paper

Ask AI

Bookmark

Key result

RGS proteins, particularly RGS4 and RGS6, act as critical negative regulators of muscarinic M2 receptor signaling in the heart, serving as brakes on vagal stimulation.

Population

Preclinical models (mice expressing RGS-insensitive Gα mutant, mice lacking RGS6 or RGS4) and general review…

Design

Review

Authors

ASAdele StewartUniversity of Iowa

Discussion

Member takes

Implication

May guide RGS-targeted therapies for autonomic imbalance; leaves open clinical translation and safety.

Key Points

To review the mechanisms by which regulator of G protein signaling (RGS) proteins, especially RGS6 and RGS4, control parasympathetic regulation of cardiac pacing and electrophysiology.
Synthesized findings from transgenic mouse models lacking RGS6 or RGS4, or expressing an RGS-insensitive Gα(i2) mutant (G184S).
Evaluated electrophysiological endpoints including sinoatrial node action potential firing and acetylcholine-induced GIRK current (IKAch) kinetics.
Genetic deletion of RGS6 or RGS4 resulted in exacerbated carbachol-induced bradycardia and pronounced inhibition of sinoatrial node action potential firing.
Loss of RGS6 eliminated the rapid activation, deactivation kinetics, and current desensitization of acetylcholine-activated GIRK currents in pacemaker tissue.
RGS6 up-regulation was identified in cardiotoxic states such as doxorubicin exposure, pointing to its involvement in chemotherapy-induced atrial arrhythmias.

Structured PICO

Population

Preclinical models (mice expressing RGS-insensitive Gα(i2) mutant, mice lacking RGS6 or RGS4) and general review of RGS proteins in the heart

RGS proteins, especially RGS6, are critical regulators of parasympathetic signaling in the heart and represent potential therapeutic targets for diseases involving abnormal autonomic control.

Limitations

Potential for functional redundancy and compensatory changes in RGS protein expression resulting from loss of a single protein.
Lack of specific antibodies with corresponding genetic knockout controls makes detection of endogenous RGS proteins difficult in vivo.
In vivo significance of some effects observed in heterologous expression systems or isolated cells remains unclear.
Need for double knockout mice to investigate redundant, additive, or synergistic functions of RGS4 and RGS6.

Cite This Study

synapsesocial.com/papers/6a153f69a2f71238514e3a90 https://doi.org/10.3389/fphys.2012.00095

Also Consider

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