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Effect of sphingosine-1-phosphate on L-type calcium current and Ca(2+) transient in rat ventricular myocytes

Egom, Emmanuel Eroume-A
Author Egom, Emmanuel Eroume-A Education Division, Department of Clinical Medicine, University of Dublin/Trinity College, Dublin, Ireland. egom@ectrs.ca Egom Clinical and Translational Research Services Ltd, Halifax, NS, B3H 4R7, Canada. egom@ectrs.ca
Bae, James S H
Author Bae, James S H Department of Pharmacology, University of Oxford, Oxford, UK
Capel, Rebecca
Author Capel, Rebecca Department of Pharmacology, University of Oxford, Oxford, UK
Richards, Mark
Author Richards, Mark Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
Ke, Yunbo
Author Ke, Yunbo Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, USA
Pharithi, Rebabonye B
Author Pharithi, Rebabonye B Heart Efficiency Unit, Cardiology Department, The Adelaide and Meath Hospital, Tallaght, Dublin, Ireland
Maher, Vincent
Author Maher, Vincent Heart Efficiency Unit, Cardiology Department, The Adelaide and Meath Hospital, Tallaght, Dublin, Ireland
Kruzliak, Peter
Author Kruzliak, Peter Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho tr 1946/1, 656 91, Brno, Czech Republic. kruzliakpeter@gmail.com
Lei, Ming
Author Lei, Ming Department of Pharmacology, University of Oxford, Oxford, UK. ming.lei@pharm.ox.ac.uk

Molecular and cellular biochemistry. 2016 Aug ; 419 (1-2) : 83-92. [epub] 20160702

Mol Cell Biochem
ISSN 1573-4919 | 0300-8177
Source

Language English Country Netherlands Media print-electronic

Document type Journal Article

Persistent link https://www.medvik.cz/link/pmid27372350

Grant support
G1002647 Medical Research Council - United Kingdom
PG/11/59/29006 British Heart Foundation - United Kingdom
PG/12/21/29473 British Heart Foundation - United Kingdom
PG/14/80/31106 British Heart Foundation - United Kingdom

PubMed 27372350
DOI 10.1007/s11010-016-2752-8
PII: 10.1007/s11010-016-2752-8
Knihovny.cz E-resources

Keywords
L-type calcium current, ICa,L, P21-activated kinase 1, Pak1, Sphingosine-1-phosphate, S1P,
MeSH
Intracellular Signaling Peptides and Proteins metabolism MeSH
Myocytes, Cardiac metabolism MeSH
Rats MeSH
Lysophospholipids pharmacology MeSH
Protein Phosphatase 2 metabolism MeSH
Sphingosine analogs & derivatives pharmacology MeSH
Heart Ventricles metabolism MeSH
Calcium metabolism MeSH
Calcium Signaling drug effects MeSH
Calcium Channels, L-Type metabolism MeSH
Animals MeSH
Check Tag
Rats MeSH
Male MeSH
Animals MeSH
Publication type
Journal Article MeSH
Names of Substances
Intracellular Signaling Peptides and Proteins MeSH
Lysophospholipids MeSH
PAK1IP1 protein, human MeSH Browser
Ppp2ca protein, rat MeSH Browser
Protein Phosphatase 2 MeSH
Sphingosine MeSH
sphingosine 1-phosphate MeSH Browser
Calcium MeSH
Calcium Channels, L-Type MeSH

Modulation of Ca(2+) homoeostasis in cardiac myocytes plays a major role in beat-to-beat regulation of heart function. Previous studies suggest that sphingosine-1-phosphate (S1P), a biologically active sphingomyelin metabolite, regulates Ca(2+) handling in cardiac myocytes, but the underlying mechanism is unclear. In the present study, we tested the hypothesis that S1P-induced functional alteration of intracellular Ca(2+) handling includes the L-type calcium channel current (ICa,L) via a signalling pathway involving P21-activated kinase 1 (Pak1). Our results show that, in rat ventricular myocytes, S1P (100 nM) does not affect the basal activity of ICa,L but is able to partially reverse the effect of the β-adrenergic agonist Isoproterenol (ISO, 100 nM) on ICa,L. S1P (25 nM) also significantly prevents ISO (5 nM)-induced Ca(2+) waves and diastolic Ca(2+) release in these cells. Our further molecular characterisation demonstrates that Pak1 activity is increased in myocytes treated with S1P (25 nM) compared with those myocytes without treatment of S1P. By immunoprecipitation we demonstrate that Pak1 and protein phosphatase 2A (PP2A) are associated in ventricular tissue indicating their functional interaction. Thus the results indicate that S1P attenuates β-adrenergic stress-induced alteration of intracellular Ca(2+) release and L-type Ca(2+) channel current at least in part via Pak1-PP2A-mediated signalling.

Department of Chemical Drugs Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Palackeho tr 1946 1 656 91 Brno Czech Republic

Department of Pharmacology University of Oxford Oxford UK

Department of Physiology Anatomy and Genetics University of Oxford Oxford UK

Department of Physiology and Biophysics University of Illinois at Chicago Chicago USA

Education Division Department of Clinical Medicine University of Dublin Trinity College Dublin Ireland

Egom Clinical and Translational Research Services Ltd Halifax NS B3H 4R7 Canada

Heart Efficiency Unit Cardiology Department The Adelaide and Meath Hospital Tallaght Dublin Ireland

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