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The reverse mode of the Na$^+$/Ca$^{2+}$ exchanger contributes to the pacemaker mechanism in rabbit sinus node cells

Tóth, Noémi; Loewe, Axel ORCID iD icon 1; Szlovák, Jozefina; Kohajda, Zsófia; Bitay, Gergő; Levijoki, Jouko; Papp, Julius Gy; Varró, András; Nagy, Norbert
1 Institut für Biomedizinische Technik (IBT), Karlsruher Institut für Technologie (KIT)

Abstract:

Sinus node (SN) pacemaking is based on a coupling between surface membrane ion-channels and intracellular Ca$^{2+}$-handling. The fundamental role of the inward Na$^+$/Ca$^{2+}$ exchanger (NCX) is firmly established. However, little is known about the reverse mode exchange. A simulation study attributed important role to reverse NCX activity, however experimental evidence is still missing. Whole-cell and perforated patch-clamp experiments were performed on rabbit SN cells supplemented with fluorescent Ca$^{2+}$-tracking. We established 2 and 8 mM pipette NaCl groups to suppress and enable reverse NCX. NCX was assessed by specific block with 1 μM ORM-10962. Mechanistic simulations were performed by Maltsev–Lakatta minimal computational SN model. Active reverse NCX resulted in larger Ca$^{2+}$-transient amplitude with larger SR Ca$^{2+}$-content. Spontaneous action potential (AP) frequency increased with 8 mM NaCl. When reverse NCX was facilitated by 1 μM strophantin the Ca$^{2+}$$_i$ and spontaneous rate increased. ORM-10962 applied prior to strophantin prevented Ca$^{2+}$$_i$ and AP cycle change. Computational simulations indicated gradually increasing reverse NCX current, Ca$^{2+}$$_i$ and heart rate with increasing Na$^+$$_i$. ... mehr


Verlagsausgabe §
DOI: 10.5445/IR/1000154473
Veröffentlicht am 13.01.2023
Originalveröffentlichung
DOI: 10.1038/s41598-022-25574-8
Scopus
Zitationen: 2
Web of Science
Zitationen: 2
Dimensions
Zitationen: 2
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biomedizinische Technik (IBT)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2022
Sprache Englisch
Identifikator ISSN: 2045-2322
KITopen-ID: 1000154473
Erschienen in Scientific Reports
Verlag Nature Research
Band 12
Seiten Art.-Nr.: 21830
Vorab online veröffentlicht am 17.12.2022
Nachgewiesen in Dimensions
Web of Science
Scopus
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