Two developmental switches in GABAergic signalling: the K+–Cl− cotransporter KCC2 and carbonic anhydrase CAVII

摘要: GABAergic signalling has the unique property of ‘ionic plasticity’, which is based on short-term and long-term changes in Cl− HCO3− ion concentrations postsynaptic neurones. While ionic plasticity caused by activity-dependent, channel-mediated anion shifts, depends expression patterns kinetic regulation molecules involved homeostasis. During development efficacy also qualitative nature (depolarization/excitation versus hyperpolarization/inhibition) transmission influenced neuronal two key molecules: chloride-extruding K+–Cl− cotransporter KCC2, cytosolic carbonic anhydrase (CA) isoform CAVII. In rat hippocampal pyramidal neurones, a steep up-regulation KCC2 accounts for ‘developmental switch’, converts depolarizing excitatory GABA responses immature neurones to classical hyperpolarizing inhibition end second postnatal week. The hippocampus generates large-scale network activity, abolished parallel consequent increase extrusion. At around day 12 (P12), an abrupt, intrapyramidal CAVII takes place, promoting evoked intense activity. This largely potassium transient resulting spatially widespread depolarization synchronous spike discharges. These facts point as putative target CA inhibitors that are used antiepileptic drugs. adult down-regulated following epileptiform activity and/or damage BDNF/TrkB signalling. lifetime membrane-associated very short, range tens minutes, makes ideally suited mediating plasticity. addition, factors influencing trafficking modulation well activation/deactivation obvious candidates responses. down-regulation under pathophysiological conditions (epilepsy, damage) mature seems reflect ‘recapitulation’ early developmental mechanisms, may be prerequisite re-establishment connectivity damaged brain tissue.