Key result
The Galpha(i2)G184S mutation, which disrupts RGS protein binding, enhanced the potency of muscarinic-mediated bradycardia up to fivefold in isolated hearts compared with wild type.
Why the study?
Does the loss of RGS protein inhibitory action on Galpha(i2) potentiate muscarinic inhibition of cardiac automaticity and conduction in isolated mouse hearts?
Population
Isolated, perfused hearts from knock-in mice with a genomic GalphaG184S point mutation and wild type
Comparison
Carbachol and A-adenosine receptor agonist, with… vs Wild type (+/+) isolated hearts
Design
Preclinical
Authors
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May implicate RGS-Gαi2 in sinus node dysfunction; leaves open human translation from mouse hearts.
Does the loss of RGS protein inhibitory action on Galpha(i2) potentiate muscarinic inhibition of cardiac automaticity and conduction in isolated mouse hearts?
Loss of endogenous RGS protein inhibition on Galpha(i2) significantly potentiates muscarinic-mediated bradycardia and AV block, suggesting a potential mechanism in sick sinus syndrome and pathological AV block.
Fu et al. (2007) studied Sick sinus syndrome and AV block. Galpha(i2)G184S (GS) point mutation vs. Wild type (+/+) mice was evaluated on Muscarinic-mediated bradycardia. The Galpha(i2)G184S mutation, which disrupts RGS protein binding, enhanced the potency of muscarinic-mediated bradycardia up to fivefold in isolated hearts compared with wild type.
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