Authors
Pettegrew JW, Short JW, Woessner RD, Strychor S, McKeag DW, Armstrong
J, Minshew NJ, Rush AJ.
Title
The effect of lithium on the membrane molecular dynamics of normal human
erythrocytes.
Source
Biol Psychiatry 1987 Jul;22(7):857-71
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 degrees 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.