@article{3478, abstract = {1. Properties of dendritic glutamate receptor (GluR) channels were investigated using fast application of glutamate to outside-out membrane patches isolated from the apical dendrites of CA3 and CA1 pyramidal neurons in rat hippocampal slices. CA3 patches were formed (15-76 μm from the soma) in the region of messy fibre (MF) synapses, and CA1 patches (25-174 μm from the soma) in the region of Schaffer collateral (SC) innervation. 2. Dual-component responses consisting of a rapidly rising and decaying component followed by a second, substantially slower, component were elicited by 1 ms pulses of 1 mM glutamate in the presence of 10 μM glycine and absence of external Mg2+. The fast component was selectively blocked by 2-5 μM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the slow component by 30 μM D-2-amino-5-phosphonopentanoic acid (D-AP5), suggesting that the fast and slow components were mediated by the GluR channels of the L-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and NMDA type, respectively. The peak amplitude ratio of the NMDA to AMPA receptor-mediated components varied between 0.03 and 0.62 in patches from both CA3 and CA1 dendrites. Patches lacking either component were rarely observed. 3. The peak current-voltage (I-V) relationship of the fast component was almost linear, whereas the I-V relationship of the slow component showed a region of negative slope in the presence of 1 mM external Mg2+. The reversal potential for both components was close to 0 mV. 4. Kainate-preferring GluR channels did not contribute appreciably to the response to glutamate. The responses to 100 ms pulses of 1 mM glutamate were mimicked by application of 1 mM AMPA, whereas 1 mM kainate produced much smaller, weakly desensitizing currents. This suggests that the fast component is primarily mediated by the action of glutamate on AMPA-preferring receptors. 5. The mean elementary conductance of AMPA receptor channels was about 10 pS, as estimated by non-stationary fluctuation analysis. The permeability of these channels to Ca2+ was low (~5% of the permeability to Cs+). 6. The elementary conductance of NMDA receptor channels was larger, with a main conductance state of about 45 pS. These channels were 3.6 times more permeable to Ca2+ than to Cs+. 7. AMPA receptor-mediated currents activated rapidly in response to 1 ms pulses of 1 mM glutamate and deactivated with a predominant, fast time constant and a smaller, slower component (τ1≃2 ms, τ2≃8 ms, contributing ~80 and ~20% to the total decay amplitude, respectively). Desensitization of the current during a 100 ms pulse was best fitted by two time constants (τ1≃10 ms, ~60%; τ2≃34 ms, ~40%). 8. NMDA receptor-mediated currents in response to 1 ms pulses of 1 mM glutamate activated and deactivated much more slowly than AMPA receptor-mediated currents. The time course could be described by a single exponential rising phase (τ≃7 ms) followed by a double exponential decay (τ1≃200 ms, ~80%; τ2≃1-3 s, ~20%). 9. Mg2+ blocked the NMDA component in a voltage-dependent manner, with a half-maximal inhibitory concentration (IC50) of 21 μM at -80 mV. At physiological Mg2+ concentrations, block of the NMDA component could be rapidly relieved with voltage jumps from negative to positive potentials. Block of the current upon return to negative potentials occurred almost instantaneously. 10. Zn2+ also selectively-blocked the NMDA receptor-mediated current with an IC50 of 22 μM, but this block differed from that of Mg2+ in that it showed little voltage dependence. Rapid application of Zn2+ together with glutamate produced partial block of the current. More block was observed if Zn2+ and glutamate were co-applied when NMDA receptor channels were already open. 11. The functional properties of dendritic GluRs were similar to those found at the soma. Knowledge of these properties facilitated simulations investigating the contribution of coactivated AMPA and NMDA receptors to synaptic depolarization and Ca2+ entry into dendritic spines. Because of its slow deactivation, the NMDA receptor-mediated current contributes substantially to depolarization and Ca2+ entry and is susceptible to modulation over a period of seconds, either by backpropagating action potentials or by the release of Zn2+ from presynaptic boutons.}, author = {Spruston, Nelson and Jonas, Peter M and Sakmann, Bert}, issn = {0022-3751}, journal = {Journal of Physiology}, number = {Pt 2}, pages = {325 -- 352}, publisher = {Wiley-Blackwell}, title = {{Dendritic glutamate receptor channels in rat hippocampal CA3 and CA1 pyramidal neurons}}, doi = {10.1113/jphysiol.1995.sp020521}, volume = {482}, year = {1995}, }