ArticlePloS one2011
Gαi2- and Gαi3-specific regulation of voltage-dependent L-type calcium channels in cardiomyocytes.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Opposite effects of GαNaunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Mu Opioid Receptor Positive Allosteric Modulator BMS-986122 Confers Agonist-Dependent G Protein Subtype Signaling Bias.Biochemistry · 2025Article
- Protective effects of GαNaunyn-Schmiedeberg's archives of pharmacology · 2024Article
- GαOncotarget · 2018Article
- Knockdown of Inhibitory Guanine Nucleotide Binding Protein Giα-2 by Antisense Oligodeoxynucleotides Attenuates the Development of Hypertension and Tachycardia in Spontaneously Hypertensive Rats.Journal of the American Heart Association · 2016Article
- Blunted apoptosis of erythrocytes in mice deficient in the heterotrimeric G-protein subunit Gαi2.Scientific reports · 2016Article
- Lack of Gαi2 leads to dilative cardiomyopathy and increased mortality in β1-adrenoceptor overexpressing mice.Cardiovascular research · 2015Article
- Platelet Gi protein Gαi2 is an essential mediator of thrombo-inflammatory organ damage in mice.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Insulin secretion stimulated by L-arginine and its metabolite L-ornithine depends on Gα(i2).American journal of physiology. Endocrinology and metabolism · 2014Article
- Conditional disruption of interactions between Gαi2 and regulator of G protein signaling (RGS) proteins protects the heart from ischemic injury.BMC pharmacology & toxicology · 2014Article
- Gαi2- and Gαi3-deficient mice display opposite severity of myocardial ischemia reperfusion injury.PloS one · 2014Article
- Gap junction modulation and its implications for heart function.Frontiers in physiology · 2014Review
- The Role of Inhibitory G Proteins and Regulators of G Protein Signaling in the in vivo Control of Heart Rate and Predisposition to Cardiac Arrhythmias.Frontiers in physiology · 2012Article
Corrections and comments
- Erratum issuedBjrnbaumer, Lutz [added]
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTwo pertussis toxin sensitive G(i) proteins, G(i2) and G(i3), are expressed in cardiomyocytes and upregulated in heart failure. It has been proposed that the highly homologous G(i) isoforms are functionally distinct. To test for isoform-specific functions of G(i) proteins, we examined their role in the regulation of cardiac L-type voltage-dependent calcium channels (L-VDCC).
methodsVentricular tissues and isolated myocytes were obtained from mice with targeted deletion of either Gα(i2) (Gα(i2) (-/-)) or Gα(i3) (Gα(i3) (-/-)). mRNA levels of Gα(i/o) isoforms and L-VDCC subunits were quantified by real-time PCR. Gα(i) and Ca(v)α(1) protein levels as well as protein kinase B/Akt and extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation levels were assessed by immunoblot analysis. L-VDCC function was assessed by whole-cell and single-channel current recordings.
resultsIn cardiac tissue from Gα(i2) (-/-) mice, Gα(i3) mRNA and protein expression was upregulated to 187 ± 21% and 567 ± 59%, respectively. In Gα(i3) (-/-) mouse hearts, Gα(i2) mRNA (127 ± 5%) and protein (131 ± 10%) levels were slightly enhanced. Interestingly, L-VDCC current density in cardiomyocytes from Gα(i2) (-/-) mice was lowered (-7.9 ± 0.6 pA/pF, n = 11, p<0.05) compared to wild-type cells (-10.7 ± 0.5 pA/pF, n = 22), whereas it was increased in myocytes from Gα(i3) (-/-) mice (-14.3 ± 0.8 pA/pF, n = 14, p<0.05). Steady-state inactivation was shifted to negative potentials, and recovery kinetics slowed in the absence of Gα(i2) (but not of Gα(i3)) and following treatment with pertussis toxin in Gα(i3) (-/-). The pore forming Ca(v)α(1) protein level was unchanged in all mouse models analyzed, similar to mRNA levels of Ca(v)α(1) and Ca(v)β(2) subunits. Interestingly, at the cellular signalling level, phosphorylation assays revealed abolished carbachol-triggered activation of ERK1/2 in mice lacking Gα(i2).
conclusionOur data provide novel evidence for an isoform-specific modulation of L-VDCC by Gα(i) proteins. In particular, loss of Gα(i2) is reflected by alterations in channel kinetics and likely involves an impairment of the ERK1/2 signalling pathway.
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