The role of Zn2+ in shaping intracellular Ca2+ dynamics in the heart

Figures

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  Figure 1.. Zn2+ transporters in the heart. (A) Localization of zinc transporters in the heart. ZIP transporters are illustrated in blue on the left of the image while ZnT transporters are colored in red on the right of the image. Transporters with confirmed protein expression through the Human Protein Atlas or reported in published Western blot/immunofluorescent in heart tissue homogenates, isolated cardiomyocytes, or cardiac cell lines (such as H9C2 cells) were included. rER, rough ER; TGN, trans-Golgi network. Created with BioRender.com. (B) RNA expression of Zn2+ transporters in normalized protein-coding transcripts per million (nTPM) in human heart. Figure was created using information available from the Human Protein Atlas (2022), Uhlén et al. (2015), and Choi et al. (2018).

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  Figure 2.. RNA expression of S/ER-located Zn2+ transporters. (A) Mean reads per kilobase of transcript per million reads mapped (RPKM) of Zn2+ transporters in human heart (RNA sequencing [RNA-Seq] data from Fagerberg et al., 2014). (B) Mean RPKM of Zn2+ transporters in rat heart (21 wk; RNA-Seq data from Yu et al., 2014). (C) Mean RPKM of Zn2+ transporters in mouse heart (RNA-Seq data from Yue et al., 2014).

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  Figure 3.. Possible Zn2+ binding sites on MG23. Partial sequence alignment of human zinc transporters ZIP1, ZIP2, and ZIP3 illustrating the conserved Zn2+ binding motif, H-x-x-x-E. Histidine residues (H) are highlighted in orange and glutamate (E) residues are highlighted in blue. This motif is also conserved across human (h), rat (r), and murine (m) MG23.

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  Figure 4.. Graphical summary of the suggested role of MG23 in cardiovascular function. MG23 may contribute to the release of Ca2+ from S/ER Ca2+ stores. In pathophysiological conditions where intracellular Zn2+ is elevated, the activity of MG23 will be increased, leading to increased release of Ca2+ from the S/ER. Increased [Zn2+]i will result in activation of RyR2. Dotted lines and question marks suggest putative interactions/functions. Figure created with BioRender.com.