Intracellular spermine confers rectification on rat calcium‐permeable AMPA and kainate receptors.

Abstract

1. Whole‐cell recordings were made from cerebellar granule cells cultured in high‐K+ medium to induce expression of Ca(2+)‐permeable AMPA receptors. Current‐voltage (I‐V) plots of agonist‐evoked responses showed varying degrees of inward rectification, but became linear within 5‐10 min. 2. Recombinant Ca(2+)‐permeable kainate receptors, composed of GluR6(Q)/KA‐2 subunits, exhibited rectifying whole‐cell I‐V plots that became linear in outside‐out patches. 3. Loss of rectification in granule cells was prevented by including 100 microM spermine in the pipette; the degree of rectification was then correlated with Ca2+ permeability. 4. Spermine also prevented loss of rectification in patches containing GluR6(Q)/KA‐2 receptors (IC50, 1.7 microM). 5. We suggest that spermine, or a similar cellular constituent, may act as a cytoplasmic factor conferring inward rectification on Ca(2+)‐permeable non‐NMDA receptors, and that ‘washout’ of this factor underlies the observed loss of rectification.

Subunit Composition, Kinetic, and Permeation Properties of AMPA Receptors in Single Neocortical Nonpyramidal Cells

“…Patch pipettes were pulled from borosilicate glass tubing and had a resistance of 5-10 M⍀ when filled with an internal solution containing (in mM): 144 K-gluconate, 3 MgC l 2 , 0.2 EGTA, 10 H EPES, 2 ATP, 0.2 GTP, and 100 M spermine, pH 7.2-7.4, 300 mOsm. Spermine was included because it maintains the voltage dependence of AM PARs in excised patches (Bowie et al, 1995;Kamboj et al, 1995;Koh et al, 1995). All potentials were corrected for junction potential (Ϫ12 mV) (Neher, 1992).…”

GluR2 protein-protein interactions and the regulation of AMPA receptors during synaptic plasticity

“…Burnashev et al 1992;Bowie & Mayer 1995;Kamboj et al 1995). The critical importance of the appropriate physiological regulation of GluR2 has been demonstrated in mutant mice that either lack GluR2 ( Jia et al 1996) or lack GluR2 editing (e.g.…”

Chapter 13 Differential mechanisms of transmission and plasticity at mossy fiber synapses

“…Within the pore of AMPA receptors a single amino acid, the so-called Q/R site not only dictates their Ca permeability but also influences their sensitivity to block by both endogenous intracellular polyamines such as spermine and spermidine as well as externally applied polyamine toxins such as philanthotoxin (Bowie and Mayer, 1995;Kamboj et al, 1995;Koh et al, 1995; Isaac et al, in press). The interaction with intracellular polyamines is in part voltage-dependent, with block being greatest at depolarized potentials.…”

“…Traditionally most mechanisms of short-term synaptic plasticity are considered to be presynaptic in origin and typically arise from changes in the release probability due to accumulation of residual calcium loads, or exhaustion of the readily releasable pool of neurotransmitter. However, CP-AMPA receptors lacking the GluR2 subunit posses an unexpected and entirely postsynaptic form of short-term plasticity due to their susceptibility to block by intracellular polymines (Rozov et al, 1998;Rozov and Burnashev, 1999).Within the pore of AMPA receptors a single amino acid, the so-called Q/R site not only dictates their Ca permeability but also influences their sensitivity to block by both endogenous intracellular polyamines such as spermine and spermidine as well as externally applied polyamine toxins such as philanthotoxin (Bowie and Mayer, 1995;Kamboj et al, 1995;Koh et al, 1995; Isaac et al, in press). The interaction with intracellular polyamines is in part voltage-dependent, with block being greatest at depolarized potentials.…”