TY - JOUR T1 - The Lurcher Mutation Identifies δ2 as an AMPA/Kainate Receptor-Like Channel That Is Potentiated by Ca<sup>2+</sup> JF - The Journal of Neuroscience JO - J. Neurosci. SP - 5973 LP - 5980 DO - 10.1523/JNEUROSCI.20-16-05973.2000 VL - 20 IS - 16 AU - Lonnie P. Wollmuth AU - Thomas Kuner AU - Claudia Jatzke AU - Peter H. Seeburg AU - Nathaniel Heintz AU - Jian Zuo Y1 - 2000/08/15 UR - http://www.jneurosci.org/content/20/16/5973.abstract N2 - Neurodegeneration in Lurcher (Lc) mice results from constitutive activation of δ2, a subunit of ionotropic glutamate receptors (GluRs) with unknown natural ligands and channel properties. Homo-oligomeric channels of GluR-δ2 with the Lurcher mutation (GluR-δ2Lc) expressed in human embryonic kidney 293 cells showed a doubly rectifying current–voltage relation reminiscent of the block by intracellular polyamines in AMPA/kainate channels. Similarly, the fraction of the total current carried by Ca2+ was ∼2–3%, comparable with that found in Ca2+-permeable AMPA/kainate channels. Currents through GluR-δ2Lc channels were also potentiated by extracellular Ca2+ in a biphasic manner, with maximal potentiation occurring at physiological concentrations of Ca2+. We examined the functional role of the Q/R site in GluR-δ2Lc by replacing glutamine with arginine. Analogous to AMPA/kainate receptors, GluR-δ2Lc(R) channels showed no voltage-dependent block by intracellular polyamines and were nominally impermeable to Ca2+. The potentiation by Ca2+, however, remained intact. Hence, GluR-δ2Lcchannels are functionally similar to the AMPA/kainate receptor channels, consistent with the high-sequence identity shared by these subunits within the channel-lining M2 and M3 segments. Furthermore, potentiation by Ca2+ and a permeability to Ca2+ comparable with that of AMPA/kainate receptors provide a possible cause for cell death in Lurcher mice and may contribute to cerebellar long-term depression under physiological conditions. ER -