Conductance changes underlying a late synaptic hyperpolarization in hippocampal CA3 neurons

Academic Article


  • 1. Single-electrode current- and voltage-clamp techniques were employed to study properties of the conductance underlying an orthodromically evoked late synaptic hyperpolarization or late inhibitory postsynaptic potential (IPSP) in CA3 pyramidal neurons in the rat hippocampal slice preparation. 2. Late IPSPs could occur without preceding excitatory postsynaptic potentials at the resting membrane potential and were graded according to the strength of the orthodromic stimulus. The membrane hyperpolarization associated with the late IPSP peaked within 140-200 ms after orthodromic stimulation of mossy fiber afferents. The late IPSP returned to base line with a half-decay time of ~200 ms. 3. As determined from constant-amplitude hyperpolarizing-current pulses, the membrane conductance increase during the late IPSP, and the time course of its decay, were similar whether measurements were made near the resting membrane potential or when the cell was hyperpolarized by ~35 mV. 4. When 1 mM cesium was added to the extracellular medium to reduce inward rectification, late IPSPs could be examined over a range of membrane potentials from -60 to -140 mV. For any given neuron, the late IPSP amplitude-membrane potential relationship was linear over the same range of membrane potentials for which the slope input resistance was constant. The late IPSP reversed symmetrically near -95 mV. 5. Intracellular injection of ethyleneglycol-bis-(β-aminoethylether)-N,N'-tetraacetic acid or extracellular application of forskolin, procedures known to reduce or block certain calcium-dependent potassium conductances in CA3 neurons, had no significant effect on the late IPSP. 6. Single-electrode voltage-clamp techniques were used to analyze the time course and voltage sensitivity of the current underlying the late IPSP. This current [the late inhibitory postsynaptic current (IPSC)] began as early as 25 ms after orthodromic stimulation and reached a peak 120-150 ms following stimulation. 7. The late IPSC decayed with a single exponential time course (τ = 185 ms). 8. A clear reversal of the late IPSC at approximately -99 mV was observed in a physiological concentration of extracellular potassium (3.5 mM). 9. Neither the slope conductance nor the time course of decay of the late IPSC was voltage dependent over the range of membrane potentials that were examined (-55 to -140 mV). The reversal potential of the response became less negative after perfusion of 6.5 mM potassium. This potassium elevation did not affect the time course or voltage dependence of the late IPSC. 10. These experiments illustrate that the conductance of the late IPSP is not activated by changes in membrane potential and thus support the hypothesis that the potassium conductance of the late IPSP is gated by a neurotransmitter.
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    Author List

  • Hablitz JJ; Thalmann RH
  • Start Page

  • 160
  • End Page

  • 179
  • Volume

  • 58
  • Issue

  • 1