LITHIUM IONS HAVE LIMITED INTRACELLULAR ACCESS - IMPLICATIONS FOR CELL REGULATION AND PHARMACOLOGY

Lithium is absorbed into the body via a paracellular route in the inte stinal mucosa. This route is also followed by other metals and the tru e function of 'transport proteins' identified for some metals is quest ioned. Lithium concentrations in cells, determined by NMR and AAS tech niques are lower than usually assumed, often no more than 10% of the e xternal concentration. This has implications for the cellular actions of lithium in therapy and its postulated mode of action. A hypothesis is proposed for an integrative and regulatory role of metals associate d with the cell membrane. It is suggested that those metals which are embedded in, and interacting with, the largely insulating lipid and gl ycolipid layers of the cell membrane might regulate charge movements i n the membrane in a manner analagous to metal particles in a silicon m icrochip. The concept is suggested of the 'biomicrochip', based on the cell membrane and with infinitely variable architecture for cellular integration and regulation.