GLUTAMATE RECEPTOR CHANNELS IN ISOLATED PATCHES FROM CA1 AND CA3 PYRAMIDAL CELLS OF RAT HIPPOCAMPAL SLICES

被引:239
作者
JONAS, P
SAKMANN, B
机构
[1] Max-Planck-Institut für Medizinische Forschung, Abteilung Zellphysiologie, Heidelberg
来源
JOURNAL OF PHYSIOLOGY-LONDON | 1992年 / 455卷
关键词
D O I
10.1113/jphysiol.1992.sp019294
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. Currents activated by glutamate receptor (GluR) agonists were recorded from outside-out patches isolated from the soma of visually identified pyramidal neurones of the CA3 and CA1 region of rat hippocampal slices. Alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), L-glutamate (L-Glu), and kainate (KA) were delivered either by bath application through perfusion of the recording chamber or by rapid application via a piezo-driven two-barrelled fast application system. 2. Bath application of each of the three agonists activated inward currents in all patches (n = 134) at holding potentials of -50 or -60 mV. The current amplitude increased in size between 3 to 30-mu-M-AMPA and 100-mu-M to 1 mM-KA. With this slow mode of bath application, the responses showed no apparent desensitization even at saturating concentrations of AMPA (30-mu-M) and KA (1 mM). 3. The ratio of currents activated by 30-mu-M-AMPA and 300-mu-M-KA showed a characteristic difference between CA3 and CA1 neurones. The ratio was 0.242 +/- 0.028 (mean +/- S.E.M., n = 16) for CA3 cell patches and 0.097 +/- 0.012 (n = 8) for CA1 cell patches indicating that GLuRs in the two cell populations are different. 4. The steady-state current-voltage relations (I-Vs) for AMPA- and KA-activated currents showed pronounced outward rectification for both cell types (when the main cations are Na+ in the bath and Cs+ in the pipette solution). The current reversed close to 0 mV and the ratio of chord conductances 80 mV on either side of the reversal potential was 2.66 for KA-activated currents in CA3 cell patches and 2.60 in CA1 cell patches. AMPA-activated currents showed a time-dependent increase after steps to positive membrane potentials and a decrease after steps to negative voltages, indicating that a gating process is responsible for outward rectification of the steady-state I-V. 5. The permeability (P) of GluR channels was high for Na+ as compared to Cs+ for both cell types (P(Na)/P(Cs) = 0.88 and 0.84). The permeability was low for N-methyl-D-glucamine+ (P(NMG)/P(Cs) less-than-or-equal-to 0.03) and Ca2+ (P(Ca)/P(Cs) less-than-or-equal-to 0.05). 6. The current noise level increased during application of AMPA or KA. Apparent single-channel conductances obtained from fluctuation analysis were higher for AMPA than for KA, but similar for both cell types. In CA3 cell patches, AMPA activated channels with an apparent chord conductance of 7.2 pS. KA of 3.0 pS conductance. 7. Fast agonist application revealed desensitization of GluR channels which was dependent on the type of agonist. Currents activated by AMPA and L-Glu rose rapidly to a peak and then desensitized to a steady-state current. In contrast, currents activated by fast application of KA rose to a plateau and did not desensitize. The steady-state current expressed as a percentage of the peak current was higher for L-Glu than for AMPA and slightly higher for CA3 than for CA1 cell patches. For CA3 cell patches, this fraction amounted to 6.2 % with 300-mu-M-L-Glu and 2.8 % with 300-mu-M-AMPA. For CA1 cell patches, corresponding values were 3.6 and 1.9 %. 8. The dose-response relations for the peak current activated by AMPA and L-Glu and the steady-state current activated by KA were similar for CA3 and CA1 cell patches. The order of potency was AMPA > L-Glu almost-equal-to KA for both cell types (EC50 values 189, 342 and 344-mu-M for CA3 cell patches and 183, 424 and 474-mu-M for CA1 cell patches). In all cases, the Hill coefficients ranged between 1.2 and 1.7. 9. The rise of AMPA and L-Glu-activated currents became faster with increasing agonist concentration for both cell types. With L-Glu, rise times decreased from about 3 ms at 100-mu-M to 500-mu-s at 3 mm. The decay for agonist concentrations greater-than-or-equal-to 300-mu-M was described by the sum of two exponential functions. The time constant of the predominant fast component was slightly concentration dependent and decreased from about 12 ms at 300-mu-M to 8 ms at 3 MM-L-Glu. 10. The current-voltage relations of the peak currents activated by 300-mu-M-AMPA were linear for both cell types with a reversal potential close to 0 mV. 11. It is concluded that the GluR channels in pyramidal cells of hippocampal CA3 and CA1 regions are distinct but share many pharmacological and functional properties. Comparison of the properties of native and recombinant GluRs suggests that in both CA3 and CA1 regions GluR channels are hetero-oligomers containing the GluR-B subunit.
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页码:143 / 171
页数:29
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