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Inter-species differences in the response of sinus node cellular pacemaking to changes of extracellular calcium

Loewe, Axel; Lutz, Yannik; Nagy, Norbert; Fabbri, Alan; Schweda, Christoph; Varró, András; Severi, Stefano

Changes of serum and extracellular ion concentrations occur regularly in patients with chronic kidney disease (CKD). Recently, hypocalcemia, i.e. a decrease of the extracellular calcium concentration $[Ca^{2+}]_o$, has been suggested as potential pathomechanism contributing to the unexplained high rate of sudden cardiac death (SCD) in CKD patients. In particular, there is a hypothesis that hypocalcaemia could slow down natural pacemaking in the human sinus node to fatal degrees. Here, we address the question whether there are inter-species differences in the response of cellular sinus node pacemaking to changes of $[Ca^{2+}]_o$. Towards this end, we employ computational models of mouse, rabbit and human sinus node cells. The Fabbri et al. human model was updated to consider changes of intracellular ion concentrations. We
identified crucial inter-species differences in the response of cellular pacemaking in the sinus node to changes of $[Ca^{2+}]_o$ with little changes of cycle length in mouse and rabbit models (<83 ms) in contrast to a pronounced bradycardic effect in the human model (up to >1000 ms). Our results suggest that experiments with human sinus node cells are required to investigate the potential mechanism of hypocalcaemia-induced bradycardic SCD in CKD patients and small animal models are not well suited.

Volltext §
DOI: 10.5445/IR/1000099115
Veröffentlicht am 18.10.2019
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biomedizinische Technik (IBT)
Sonderforschungsbereich 1173 (SFB 1173)
Publikationstyp Forschungsbericht/Preprint
Publikationsjahr 2019
Sprache Englisch
Identifikator ISSN: 2365-662X
KITopen-ID: 1000099115
Verlag Karlsruher Institut für Technologie (KIT)
Umfang 4 S.
Serie CRC 1773 ; 2019/16
Projektinformation SFB 1173/2 (DFG, DFG KOORD, SFB 1173/2 2019)
Schlagwörter rabbits, mice, extracellular, ions, Calcium, data models, cats
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