Effects of lithium on electrical activity and potassium ion distribution in the vertebrate central nervous system.
Three different regions of the vertebrate central nervous system maintained in vitro (frog spinal cord, guinea pig olfactory cortex and hippocampus) have been used to investigate how Li+ influences membrane potential, membrane resistance, action potentials, synaptic potentials and the transmembrane K+-distribution of neurons and glial cells. In view of the therapeutic action of Li+ in manic-depressive disease, a special effort was made to determine the threshold concentration for the actions of Li+ on the parameters described above. It was observed that Li+ induced a membrane depolarization of both neurons and glial cells, a decrease of action potential amplitudes, a facilitation of monosynaptic excitatory postsynaptic potentials and a depression of polysynaptic reflexes. The membrane resistance of neurons was not altered. Li+ also induced an elevation of the free extracellular potassium concentration and a decrease of the free intracellular potassium concentration. Furthermore, in the presence of Li+ a slowing of the recovery of the membrane potential of neurons and glial cells, and of the extracellular potassium concentration after repetitive synaptic stimulation was observed. The threshold concentrations for the effects of Li+ were below 5 mmol/l in the frog spinal cord and below 2 mmol/l in the guinea pig olfactory cortex and hippocampus. The basic mechanism underlying the action of Li+ may be an interaction with the transport-function of the Na+/K+ pump.
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D002712:Chlorides / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects*; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D009830:Olfactory Bulb / Q000187:drug effects; D011188:Potassium / Q000378:metabolism*; D011893:Rana esculenta; D013116:Spinal Cord / Q000187:drug effects; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*
D002712:Chlorides; D007473:Ion Channels; D008094:Lithium; D018021:Lithium Chloride; D011188:Potassium