Ay. Kabakov et al., SYNAPSE-SPECIFIC ACCUMULATION OF LITHIUM IN INTRACELLULAR MICRODOMAINS - A MODEL FOR UNCOUPLING COINCIDENCE DETECTION IN THE BRAIN, Synapse, 28(4), 1998, pp. 271-279
Lithium's therapeutic specificity for the treatment of bipolar disorde
r may be attributable in part to an ability to target sites where ther
e are high levels of synaptic activity. We show that glutamate recepto
rs expressed in oocytes are highly permeable to lithium. Mathematical
simulations of Li+ diffusion in mature dendritic spines suggest that i
n the presence of 1 mM extracellular lithium one synaptic current can
increase Li+ concentration in the spine head by 4 mM with a decay time
constant of about 15-20 ms. Two or more current spikes will produce o
scillations between 6 and 8 mM or potentially higher. These results pr
edict that the local intracellular lithium in dendritic spines can ris
e to high enough levels to uncouple second messenger mechanisms of coi
ncidence detection. (C) 1998 WiIey-Liss, Inc.