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dc.contributor.authorHassinen Minna
dc.contributor.authorHaverinen Jaakko
dc.contributor.authorVornanen Matti
dc.date.accessioned2018-01-09T14:23:28Z
dc.date.available2018-01-09T14:23:28Z
dc.date.issued2017
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/5145
dc.description.abstractFunny current (If), formed by hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels), is supposed to be crucial for the membrane clock regulating the cardiac pacemaker mechanism. We examined the presence and activity of HCN channels in the brown trout (Salmo trutta fario) sinoatrial (SA) pacemaker cells and their putative role in heart rate (fH) regulation. Six HCN transcripts (HCN1, HCN2a, HCN2ba, HCN2bb, HCN3, and HCN4) were expressed in the brown trout heart. The total HCN transcript abundance was 4.0 and 4.9 times higher in SA pacemaker tissue than in atrium and ventricle, respectively. In the SA pacemaker, HCN3 and HCN4 were the main isoforms representing 35.8 ± 2.7 and 25.0 ± 1.5%, respectively, of the total HCN transcripts. Only a small If with a mean current density of −1.2 ± 0.37 pA/pF at −140 mV was found in 4 pacemaker cells out of 16 spontaneously beating cells examined, despite the optimization of recording conditions for If activity. If was not found in any of the 24 atrial myocytes and 21 ventricular myocytes examined. HCN4 coexpressed with the MinK-related peptide 1 (MiRP1) β-subunit in CHO cells generated large If currents. In contrast, HCN3 (+MiRP1) failed to produce If in the same expression system. Cs+ (2 mM), which blocked 84 ± 12% of the native If, reversibly reduced fH 19.2 ± 3.6% of the excised multicellular pacemaker tissue from 53 ± 5 to 44 ± 5 beats/min (P < 0.05). However, this effect was probably due to the reduction of IKr, which was also inhibited (63.5 ± 4.6%) by Cs+. These results strongly suggest that fH regulation in the brown trout heart is largely independent on If.en
dc.language.isoENen
dc.publisherAmerican Physiological Societyen
dc.relation.ispartofseriesAMERICAN JOURNAL OF PHYSIOLOGY. REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGYen
dc.relation.urihttp://dx.doi.org/10.1152/ajpregu.00227.2017en
dc.rightsAll rights reserveden
dc.subjectfish cardiac pacemakeren
dc.subjectHCN channelsen
dc.subjectfunny currenten
dc.subjecttranscript expressionen
dc.subjectheart rate regulationen
dc.titleSmall functional If current in sinoatrial pacemaker cells of the brown trout (Salmo trutta fario) heart despite strong expression of HCN channel transcriptsen
dc.description.versionfinal draften
dc.contributor.departmentYmpäristö- ja biotieteiden laitos / Toimintaen
uef.solecris.id49391025en
dc.type.publicationinfo:eu-repo/semantics/articleen
dc.rights.accessrights© American Physiological Societyen
dc.relation.doi10.1152/ajpregu.00227.2017en
dc.description.reviewstatuspeerRevieweden
dc.format.pagerangeR711-R722en
dc.relation.issn0363-6119en
dc.relation.volume313en
dc.rights.accesslevelopenAccessen
dc.type.okmA1en
dc.type.versioninfo:eu-repo/semantics/acceptedVersionen
uef.solecris.openaccessEi


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