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Kinetic differences between synaptic and extrasynaptic GABA(A) receptors in CA1 pyramidal cells.
1Department of Anesthesiology, University of Wisconsin, Madison, Wisconsin 53706, USA. mibanks@facstaff.wisc.edu
Summary
Two populations of GABA(A) receptors exist in CA1 pyramidal neurons. Fast synaptic receptors generate rapid inhibitory postsynaptic currents (IPSCs), while slow extrasynaptic receptors respond to exogenous GABA.
Area of Science:
- Neuroscience
- Cellular Electrophysiology
Background:
- GABA(A)-mediated inhibitory postsynaptic currents (IPSCs) typically show faster decay kinetics than responses from receptors in excised patches.
- This discrepancy has been observed in CA1 pyramidal neurons, suggesting underlying differences in receptor properties or regulation.
Purpose of the Study:
- To investigate the source of the kinetic discrepancy between synaptic and extrasynaptic GABA(A) receptor responses in CA1 pyramidal neurons.
- To determine if patch excision alters receptor properties or if distinct receptor populations exist.
Main Methods:
- Whole-cell patch-clamp recordings in CA1 pyramidal neurons.
- Application of brief pulses of GABA to excised and nucleated patches.
- Recording of spontaneous and evoked IPSCs.
- Investigation of calcium's effect on receptor responses.
Main Results:
- IPSCs decayed rapidly (tau(Decay) ≈ 18 msec), while excised patch responses to brief GABA pulses were significantly slower (tau(Decay) ≈ 63 msec).
- This difference was not due to GABA application transients or concentration.
- Nucleated patches retained fast synaptic receptor kinetics, indicating patch excision did not alter synaptic receptors.
- Elevated calcium selectively modulated patch responses to exogenous GABA but not IPSCs, suggesting distinct receptor populations.
Conclusions:
- CA1 pyramidal cells contain two distinct GABA(A) receptor populations with different kinetic properties.
- Fast synaptic receptors mediate rapid IPSCs.
- Slow extrasynaptic receptors dominate responses to exogenous GABA application in excised patches and are differentially regulated by intracellular factors like calcium.