Flip and Flop: A Cell-Specific Functional Switch in Glutamate-Operated Channels of the CNS

作者：Bernd Sommer, Kari Keinänen, Todd A. Verdoorn, William Wisden, Nail Burnashev, Anne Herb, Martin Köhler, Tamaki Takagi, Bert Sakmann, Peter H. Seeburg · 发表于：Science · 年份：1990 · DOI：10.1126/science.1699275 · 被引用次数：1268 · 研究领域：Neuroscience and Neuropharmacology Research、Ion channel regulation and function、Receptor Mechanisms and Signaling

In the central nervous system (CNS), the principal mediators of fast synaptic excitatory neurotransmission are L-glutamate-gated ion channels that are responsive to the glutamate agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). In each member of a family of four abundant AMPA receptors, a small segment preceding the predicted fourth transmembrane region has been shown to exist in two versions with different amino acid sequences. These modules, designated "flip" and "flop," are encoded by adjacent exons of the receptor genes and impart different pharmacological and kinetic properties on currents evoked by L-glutamate or AMPA, but not those evoked by kainate. For each receptor, the alternatively spliced messenger RNAs show distinct expression patterns in rat brain, particularly in the CA1 and CA3 fields of the hippocampus. These results identify a switch in the molecular and functional properties of glutamate receptors operated by alternative splicing.