ArticleProceedings of the National Academy of Sciences of the United States of America1997
Targeted inactivation of alphai2 or alphai3 disrupts activation of the cardiac muscarinic K+ channel, IK+Ach, in intact cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 53 citations in OpenAlex.
- Differential effects of inhibitory G protein isoforms on G protein-gated inwardly rectifying KAmerican journal of physiology. Cell physiology · 2018Article
- Knockdown of cardiac Kir3.1 gene with siRNA can improve bradycardia in an experimental sinus bradycardia rat model.Molecular and cellular biochemistry · 2017Article
- μ-Opioid receptor coupling to Gα(o) plays an important role in opioid antinociception.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2011Article
- Sex dimorphic actions of rosiglitazone in generalised peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-deficient mice.Diabetologia · 2010Article
- Genetic disruption of G proteins, G(i2)alpha or G(o)alpha, does not abolish inotropic and chronotropic effects of stimulating muscarinic cholinoceptors in atrium.British journal of pharmacology · 2009Article
- Targeted G-protein inhibition as a novel approach to decrease vagal atrial fibrillation by selective parasympathetic attenuation.Cardiovascular research · 2009Article
- The role of inhibitory heterotrimeric G proteins in the control of in vivo heart rate dynamics.American journal of physiology. Regulatory, integrative and comparative physiology · 2008Article
- Go but not Gi2 or Gi3 is required for muscarinic regulation of heart rate and heart rate variability in mice.Biochemical and biophysical research communications · 2007Article
- Gene-trapped mouse embryonic stem cell-derived cardiac myocytes and human genetics implicate AKAP10 in heart rhythm regulation.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Hypotension, lipodystrophy, and insulin resistance in generalized PPARgamma-deficient mice rescued from embryonic lethality.The Journal of clinical investigation · 2007Article
- Kinetic modeling of Na(+)-induced, Gbetagamma-dependent activation of G protein-gated K(+) channels.Journal of molecular neuroscience : MN · 2005Article
- Differential subunit composition of the G protein-activated inward-rectifier potassium channel during cardiac development.The Journal of clinical investigation · 2004Article
- Gating properties of GIRK channels activated by Galpha(o)- and Galpha(i)-coupled muscarinic m2 receptors in Xenopus oocytes: the role of receptor precoupling in RGS modulation.The Journal of physiology · 2002Article
- Disruption of cytoskeletal integrity impairs Gi-mediated signaling due to displacement of Gi proteins.The Journal of cell biology · 2001Article
- MEKK1 suppresses oxidative stress-induced apoptosis of embryonic stem cell-derived cardiac myocytes.Proceedings of the National Academy of Sciences of the United States of America · 1999Article
- Simultaneous Cre catalyzed recombination of two alleles to restore neomycin sensitivity and facilitate homozygous mutations.Nucleic acids research · 1999Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Cardiac muscarinic receptors activate an inwardly rectifying K+ channel, IK+Ach, via pertussis toxin (PT)-sensitive heterotrimeric G proteins (in heart Gi2, Gi3, or Go). We have used embryonic stem cell (ES cell)-derived cardiocytes with targeted inactivations of specific PT-sensitive alpha subunits to determine which G proteins are required for receptor-mediated regulation of IK+Ach in intact cells. The muscarinic agonist carbachol increased IK+Ach activity in ES cell-derived cardiocytes from wild-type cells, in cells lacking alphao, and in cells lacking the PT-insensitive G protein alphaq. In cells with targeted inactivation of alphai2 or alphai3, channel activation by both carbachol and adenosine was blocked. Carbachol-induced channel activation was restored in the alphai2- and alphai3-null cells by reexpressing the previously targeted gene and guanosine 5'-[gamma-thio] triphosphate was able to fully activate IK+Ach in excised membranes patches from these mutants. In contrast, negative chronotropic responses to both carbachol and adenosine were preserved in cells lacking alphai2 or alphai3. Our results show that expression of two specific PT-sensitive alpha subunits (alphai2 and alphai3 but not alphao) is required for normal agonist-dependent activation of IK+Ach and suggest that both alphai2- and alphai3-containing heterotrimeric G proteins may be involved in the signaling process. Also the generation of negative chronotropic responses to muscarinic or adenosine receptor agonists do not require activation of IK+Ach or the expression of alphai2 or alphai3.
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