Vol.:(0123456789) 1 3
JBIC Journal of Biological Inorganic Chemistry (2021) 26:641–658
https://doi.org/10.1007/s00775-021-01883-7
ORIGINAL PAPER
Kinetic mechanisms by which nickel alters the calcium (Ca
2+
) transport
in intact rat liver
Karina Sayuri Utsunomiya
1
· Lucas Jonatas da Silva
1
· Juliana Iwamoto
1
· Rodrigo Polimeni Constantin
1
·
Eduardo Hideo Gilglioni
1
· Jorgete Constantin
1
· Adelar Bracht
1
· Ronald Petrus Johannes Oude Elferink
2
·
Emy Luiza Ishii‑Iwamoto
1
Received: 13 May 2021 / Accepted: 14 July 2021 / Published online: 24 July 2021
© Society for Biological Inorganic Chemistry (SBIC) 2021
Abstract
In the present work, the multiple-indicator dilution (MID) technique was used to investigate the kinetic mechanisms by which
nickel (Ni
2+
) afects the calcium (Ca
2+
) transport in intact rat liver.
45
Ca
2+
and extra- and intracellular space indicators were
injected in livers perfused with 1 mM Ni
2+
, and the outfow profles were analyzed by a mathematical model. For comparative
purposes, the efects of norepinephrine were measured. The infuence of Ni
2+
on the cytosolic Ca
2+
concentration ([Ca
2+
]
c
)
in human hepatoma Huh7 cells and on liver glycogen catabolism, a biological response sensitive to cellular Ca
2+
, was also
evaluated. The estimated transfer coefcients of
45
Ca
2+
transport indicated two mechanisms by which Ni
2+
increases the
[Ca
2+
]
c
in liver under steady-state conditions: (1) an increase in the net efux of Ca
2+
from intracellular Ca
2+
stores due to
a stimulus of Ca
2+
efux to the cytosolic space along with a diminution of Ca
2+
re-entry into the cellular Ca
2+
stores; (2) a
decrease in Ca
2+
efux from the cytosolic space to vascular space, minimizing Ca
2+
loss. Glycogen catabolism activated by
Ni
2+
was transient contrasting with the sustained activation induced by norepinephrine. Ni
2+
caused a partial reduction in
the norepinephrine-induced stimulation in the [Ca
2+
]
c
in Huh7 cells. Our data revealed that the kinetic parameters of Ca
2+
transport modifed by Ni
2+
in intact liver are similar to those modifed by norepinephrine in its frst minutes of action, but
the membrane receptors or Ca
2+
transporters afected by Ni
2+
seem to be distinct from those known to be modulated by
norepinephrine.
Graphic abstract
Hepatocyte
k
3
k
4
Organelles
[Ca
2+
]
i1
[Ca
2+
]
i2
k
1
k
2
Glycocalyx
Plasma membrane
Cytosol
Hemodynamic effects
t
0
β
Glycogenolysis
V
i
Oxygen uptake [Ca
2+
]
e1
[Ca
2+
]
e2
λ
1
=∞
λ
2
=∞
Disse space
Sinusoid
[Ca
2+
]
i1
Norepinephrine action
interference
Flow
Ni
2+
NiCl
2
NiCl
2
Keywords Liver hemodynamic · Toxicity · Enzyme kinetics · Heavy metal · Ca
2+
-sensing receptor
* Emy Luiza Ishii-Iwamoto
eliiwamoto@uem.br
Extended author information available on the last page of the article