Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 7 The Erythrocyte: Physiology, Metabolism, and Biochemical Disorders
Other pathways of sodium and potassium transport
occur to variable degrees in certain species. These pathways
include passive diffusion, Na ,K ,Cl cotransport,
Na Na countertransport, band 3 anion transport as
NaCO 3
, Na -dependent amino acid transport, K ,Cl
cotransport, Na ,H exchange, and a calcium-dependent
K channel ( Contreras et al. , 1986 ; Ellory and Tucker,
1983 ; Haas, 1989 ; Maher and Kuchel, 2003 ). A negative
linear correlation between internal sodium concentration
and membrane protein-to-lipid ratio was found by comparison
of RBC values from nine mammalian species, the significance
of which is unknown ( Garnier et al. , 1984 ).
RBC volumes influence cation fluxes. Sodium flux
increases when cells are shrunken, and potassium flux
increases when cells are swollen. The Na ,K ,Cl cotransport
and Na -H exchange are activated by cell shrinkage
and K -Cl cotransport is activated by cell swelling
( Dunham, 2004 ; Haas, 1989 ; Mairbaurl and Herth, 1996 ).
Volume changes are believed to be detected from alterations
in cytoplasmic macromolecules ( Parker, 1992 ).
Early nucleated erythroid precursors in dog bone marrow
have HK content, whereas mature RBCs are of the
LK type. The switch from HK to LK content occurs
during the maturation from early to late nucleated erythroid
cells ( Kirk et al. , 1983 ). When erythropoiesis is dramatically
stimulated in response to a hemolytic anemia, much
of the HK to LK transition does not occur until after
denucleation. Consequently, stress reticulocytes, produced
in response to anemia, have potassium contents much
higher than reticulocytes normally released into blood. The
high potassium concentration in canine stress reticulocytes
results from membrane Na ,K -ATPase activity that is lost
during maturation into RBCs, possibly by ATP-dependent
proteolysis ( Inaba and Maede, 1986 ). Stress reticulocytes
produced by LK -type ruminants ( Israel et al. , 1972 ; Kim
et al. , 1980 ; Tucker and Ellory, 1971 ) also have high potassium
concentrations as a result of high Na ,K -ATPase
activities ( Blostein and Grafova, 1990 ). The decline in the
number of Na ,K pumps on LK sheep reticulocytes during
maturation is modulated by the Lp antigen ( Xu et al. ,
1994 ). Fetal and neonatal RBCs examined from mammals
with LK RBCs have higher potassium concentrations than
adult RBCs, but the difference in dogs was not as dramatic
as that in ruminants ( Coulter and Small, 1973 ; Ellory and
Tucker, 1983 ).
3 . Calcium
Excessive intracellular Ca
2
is deleterious to RBCs; consequently,
they actively extrude Ca 2 using a calcium pump
having Ca 2 -activated, Mg
2
-dependent ATPase activity.
A calcium-binding protein called calmodulin activates
the calcium pump ( Bababunmi et al. , 1991 ; Hinds and
Vincenzi, 1986 ). This pump, working in conjunction with
a Na -Ca
2
countertransport system, appears to be important
in RBC volume regulation in dogs ( Parker, 1992 ).
4 . Amino Acids
Amino acid transport in RBCs provides amino acids for
synthesis of reduced glutathione (GSH). In addition, amino
acid transporters may be responsible for efflux of amino
acids during reticulocyte maturation ( Tunnicliff, 1994 ).
Several amino acid transport systems have been recognized
in mammalian RBCs, each with its own characteristic
species distribution, ion requirements, and substrate
specificity ( Fincham et al. , 1987 ; Young, 1983 ). In addition,
the band 3 anion transporter can transport glycine
and some other amino acids ( Fincham et al. , 1987 ). A y
transport system that transports cationic amino acids has
been described in human RBCs. This system is distinct
from that of the y L system, which is a cationic amino
acid transporter that also accepts neutral amino acids with
high affinity in the presence of Na (Rojas and Deves,
1999 ). A Na -independent C amino acid transporter has
been described in sheep whose optimal substrates are cationic
amino acids and small neutral amino acids ( Young,
1983 ). Sheep deficient in this transporter have low RBC
GSH, because of impaired cysteine transport ( Tucker et al. ,
1981 ). A similar asc transport system occurs in most equine
RBCs, and deficient horses are predisposed to GSH deficiency
( Fincham et al. , 1987, 1988 ). A transport system
for cationic amino acids in cat RBCs has been called the
Ly system ( Young, 1983 ). Dog and cat RBCs have a
Na -dependent acidic amino acid transporter that optimally
transports glutamate and aspartate. The transport of
1 glutamate into dog RBCs is accompanied by 2 Na and
by the countertransport of 1 K and 1 anion ( Sato et al. ,
1994 ). A Na -dependent anionic amino acid transporter,
termed excitatory amino acid carrier 1 (EAAC1), has been
reported in rat RBC membranes ( Novak et al. , 2002 ).
5 . Glucose
Species vary in their permeability to glucose, with human
RBCs being very permeable and pig RBCs being poorly
permeable ( McManus, 1967 ). RBCs of other domestic
animals appear to be intermediate between these extremes
(Arai et al. , 1992 ; Bolis, 1973 ; Widdas, 1955 ). Facilitative
glucose transporter 1 (GLUT-1) mediates the passive diffusion
of glucose into RBCs ( Jiang et al. , 2006 ). Glucose
movement into RBCs is not regulated by insulin ( Baldwin,
1993 ). RBCs from adult pigs lack a functional glucose
transporter ( Craik et al. , 1988 ) and, therefore, have limited
ability to utilize glucose for energy ( Kim and McManus,
1971 ; Magnani et al. , 1983 ). In contrast, RBCs from neonatal
piglets and pig reticulocytes have the transporter ( Craik
et al. , 1988 ) and, consequently, exhibit substantial glucose
transport ( Kim and Luthra, 1977 ). A similar phenomenon