Reversible inhibition of GABAA receptors by α7-containing nicotinic receptors on the vertebrate postsynaptic neurons

摘要: Nicotinic acetylcholine receptors (nAChRs) are expressed throughout the central nervous system and influence a variety of higher order functions including learning memory. While effects presynaptic nAChRs on transmitter release have been well documented, little is known about possible postsynaptic actions. A major species neuronal contains α7 gene product has high relative permeability to calcium. Both rodent hippocampal interneurons chick ciliary ganglion neurons these α7-nAChRs often closely juxtaposed GABAA receptors. We show here that in both cases activation neuron acutely down-regulates GABA-induced currents. Nicotine application dissociated diminished subsequent receptor responses GABA. The effect was blocked by α7-nAChR antagonists, chelation intracellular Ca2+ with BAPTA, inhibition Ca2+–calmodulin-dependent protein kinase II mitogen-activated kinase. similar outcome obtained hippocampus where electrical stimulation activate cholinergic fibres reduced amplitude receptor-mediated inhibitory reduction showed same calcium dependence seen absent slices from knockout mice. Moreover, blockade rundown whole-cell responses, indicating ongoing endogenous modulation. results demonstrate regulation identify new mechanism which nicotinic signalling influences function.