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Vol.58 (2012) >

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Title: Inhibitory effect of β-hydroxybutyric acid on L-type Ca^{2+} current under β-adrenergic stimulation in guinea pig Cardiac ventricular myocytes
Other Titles: Ketone body activates HCA2 receptor in guinea pig cardiac myocytes
Authors: Kurihara, Masato
Akama, Youichi
Kimura, Junko
Affiliation: 薬理学講座
Source title: Fukushima Journal of Medical Science
Volume: 58
Issue: 2
Start page: 144
End page: 150
Issue Date: 2012
Abstract: Severe ketoacidosis induces heart failure and cardiac arrest, but its mechanism is unknown. Recently, hydroxy-carboxylic acid receptor 2 (HCA(2)) was found to be a receptor for a ketone body, β-hydroxybutyric acid (BHB), and is coupled with Gi-GTP binding protein. HCA(2) expression was reported in the guinea pig heart. Therefore, using guinea pig cardiac myocytes, we investigated effects of BHB on L-type Ca(2+) current pre-augmented with β-adrenoceptor agonist, isoproterenol under the whole-cell voltage clamp. BHB significantly reduced the Ca(2+) current pre-augmented with isoproterenol. The effect of BHB was concentration dependent with IC(50) of 1.1 mM. Nicotinic acid (NA), another ligand for HCA(2), also exerted an effect on the Ca(2+) current similar to that of BHB. The effects of BHB and NA were reduced by a specific Gi inhibitor, pertussis toxin in the pipette solution. Our results suggest that BHB activates Gi-coupled signal transduction pathway via HCA(2) in guinea pig cardiac myocytes. The HCA(2)-mediated signal transduction may be associated with ketoacidosis-induced cardiac suppression.
Publisher: The Fukushima Society of Medical Science
Publisher (Alternative foam): 福島医学会
language: eng
URI: http://ir.fmu.ac.jp/dspace/handle/123456789/342
Full text URL: http://ir.fmu.ac.jp/dspace/bitstream/123456789/342/1/FksmJMedSci_58_p144.pdf
ISSN: 0016-2590
DOI: 10.5387/fms.58.144
PubMed ID: 23237870
Other version: http://dx.doi.org/10.5387/fms.58.144
Rights: © 2012 The Fukushima Society of Medical Science
Appears in Collections:Vol.58 (2012)

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