Non-NMDA-type glutamate receptors play a fundamental role in fast excitatory transmission at many central synapses. While much is known about the macroscopic properties of AMPA receptors in hippocampal CA1 cells (Spruston et al. 1995), the single-channel properties of their AMPA- and kainate (KA)-receptors have received less attention. Because of this, it has been difficult to relate the properties of synaptic non-NMDA channels with single-channel behaviour in these cells.

Steady-state recordings of single-channel currents were obtained by applying glutamate (Glu), AMPA or KA, to outside-out patches from CA1 cells in rat hippocampal slices from humanely killed animals. Two types of events were apparent in the presence of these agonists: short duration events with open-times < 500 ms, and long duration events with open times > 1 ms. Whereas both types of event could be blocked with the non-NMDAR antagonist CNQX, long duration openings were more sensitive to the AMPAR-selective blocker GYKI, suggesting that they arose from AMPARs. Consistent with this idea, we found differences between the channel openings activated by KA and AMPA/Glu. A majority of events activated by 30Ð100 mM KA were short duration type; the small percentage (< 10 %) of long duration events activated by KA gave a mean open time of 1.2 ms (n = 3 patches). On the other hand, AMPA and Glu activated predominantly long duration openings with open times up to 50 ms (mean ± S.D. 3.8 ± 0.8 ms, n = 4). The majority of conductance levels activated by Glu, AMPA and KA were in the range 4Ð10 pS; other conductance levels were also discernible but less frequent. However, at high glutamate concentrations (10-20 mM), channel openings with slope conductances of 13.6 and 16.6 pS became prevalent. During an individual long duration opening, channels displayed up to four different conductance levels. Other levels were also apparent within recordings. This suggests either that additional channel types were present or that channels could open to other levels.

In conclusion, we have identified two functionally distinct types of non-NMDAR channel in CA1 cells. The conductance values we have obtained from directly resolved single AMPAR channels are consistent with estimates of weighted mean channel conductance derived from non-stationary fluctuation analysis of glutamate-evoked responses in patches (~10Ð12 pS; Spruston et al. 1995; Banke et al. 2000), and estimates from synaptic AMPAR channels (4Ð10 pS; Benke et al. 1998) in these cells.

This work was supported by The Wellcome Trust.

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