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Abstract
Erythrocytes from normal adults with no personal or family history of bipolar affective
disorder were analyzed by fluorescence spectroscopy to determine what effect, if any,
acute in vitro incubation with lithium had on erythrocyte membrane dynamics. The effects
on erythrocyte membrane molecular dynamics of varying concentrations of Li2CO3 (0.25–2.0 meq/liter), varying incubation temperatures (25–40°C), and varying incubation
times (5–185 min) were investigated. Following incubation with Li2CO3, the erythrocytes were labeled with either 4-phenylspiro-[furan-2(3H),−1′phthalan]−3,3′-dione
(fluorescamine), which binds to membrane surface primary amines, or 12(9)anthroyl
stearate [12(9)AS], which inserts deep in the membrane hydrocarbon core. The membrane
molecular dynamics were then determined by fluorescence anisotropy measurements. These
studies demonstrate that clinically relevant concentrations of Li+ incubated with intact normal human erythrocytes significantly alters molecular dynamics
on the erythrocyte membrane surface, with less striking changes in the hydrocarbon
core. A possible interpretation of these findings is that hydrated Li+ alters the electrostatic interaction of membrane surface molecules, as well as the
surrounding solvent (water) structure, with a resultant increase in the molecular
motion of these molecules. Alterations in membrane receptor motion could potentially
alter receptor functional activity. If similar motional alterations were to occur
in the interior of a membrane channel, such as an ionophore, the functional activity
of the channel could also be potentially altered. These findings provide additional
insight into possible biological actions of Li +, as well as potential molecular alterations in bipolar affective disorder erythrocytes.
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Article info
Publication history
Received in revised form:
September 25,
1986
Received:
September 30,
1985
We would like to thank Dr. David J. Kupfer for critically reading the manuscript and for helpful suggestions. Dr. George Zubenko for performing the lifetime measurements, and Mary Solarczyk for her secretarial assistance in preparing this manuscript.Footnotes
☆Supported in part by a grant from the United Cerebral Palsy Foundation, by NIA Grants 1R01 AG05657 and AG05133-01A1 and by CRC Grant MH 30915.
☆☆We would like to thank Dr. David J. Kupfer for critically reading the manuscript and for helpful suggestions. Dr. George Zubenko for performing the lifetime measurements, and Mary Solarczyk for her secretarial assistance in preparing this manuscript.
Identification
Copyright
© 1987 Published by Elsevier Inc.
