Lithium (Li+) has been used as a first-line drug in the treatment of bipolar disorder for more than six decades. Despite extensive research the therapeutic mechanism of action of Li+ remains unknown. A large body of recent evidence from genetic linkage, genome-wide association, and pathways-based analytical studies have implicated neuronal membrane ion channels in bipolar disorder. Evidence from few in vitro biophysical studies using Li+ have also indicated possible membrane effects of Li+, but no specific ion channel targets have been identified. In addition, selected antiepileptic drugs with established ion channel blocking effects are used as alternatives to or in combination with Li+, to treat bipolar disorder. Substantial evidence therefore suggests that bipolar disorder might be a ‘channelopathy’, and that Li+ might mediate its therapeutic effect by acting on membrane ion channels.
My study sought to identify possible post-synaptic membrane ion channel target(s) of Li+ in projection neurons within the limbic system, using olfactory bulb mitral cells as an in vitro model. My presentation will mainly focus on a prominent subthreshold membrane effect of Li+, mediated by blockade of a subthreshold K+ current similar to ID (the delay current defined in several types of brain neuron). It will also briefly address the role of glycogen synthase kinase-3 (GSK3) in Li+ action, and attempt to compare the effects of Li+ with other first-line bipolar drugs.
|Date||Wednesday, 14 November 2018|
|Time||3:00pm - 4:00pm|
|Event Category||Health Sciences|
|Location||Hercus d'Ath Lecture Theatre, Great King Street|