EPSPs in rat neocortical neurons in vitro. II. Involvement of N-methyl-D-aspartate receptors in the generation of EPSPs

1. Intracellular recordings were obtained from neurons in layer
II/III of rat frontal cortex. Single-electrode current- and
voltage-clamp techniques were employed to compare the sensitivity
of excitatory postsynaptic potentials (EPSPs) and iontophoretically
evoked responses to N-methyl-D-aspartate (NMDA) to the selective
NMDA antagonist D-2-amino-5-phosphonovaleric acid (D-2-APV). The
voltage dependence of the amplitudes of the EPSPs before and after
pharmacologic changes in the neuron's current-voltage relationship
was also examined. 2. NMDA depolarized the membrane potential,
increased the neuron's apparent input resistance (RN), and evoked
bursts of action potentials. The NMDA-induced membrane current
(INMDA) gradually increased with depolarization from -80 to -40 mV.
The relationship between INMDA and membrane potential displayed a
region of negative slope conductance in the potential range between
-70 and -40 mV which was sufficient to explain the apparent
increase in RN and the burst discharges during the NMDA-induced
depolarization. 3. Short-latency EPSPs (eEPSPs) were evoked by
low-intensity electrical stimulation of cortical layer IV. Changes
in the eEPSP waveform following membrane depolarization and
hyperpolarization resembled those of NMDA-mediated responses.
However, the eEPSP was insensitive to D-2-APV applied at
concentrations (up to 20 microM) that blocked NMDA responses. 4.
EPSPs with latencies between 10 and 40 ms [late EPSPs (lEPSPs)]
were evoked by electrical stimulation using intensities just
subthreshold to the activation of IPSPs. The amplitude of the lEPSP
increased with hyperpolarization and decreased with depolarization.
5. The lidocaine derivative QX-314, injected intracellularly,
suppressed sodium-dependent action potentials and depolarizing
inward rectification. Simultaneously, the amplitude of the eEPSP
significantly decreased with depolarization. Neither the amplitude
of a long-latency EPSP nor the amplitude of inhibitory postsynaptic
potentials (IPSPs) was significantly affected by QX-314. 6. Cesium
ions (0.5-2.0 mM) added to the bathing solution reduced or blocked
hyperpolarizing inward rectification. Under these conditions, the
amplitude of the eEPSP increased with hyperpolarization. The
amplitude of the lEPSP was unaltered or enhanced. 7. The lEPSP was
reversibly blocked by D-2-APV (5-20 microM), although the
voltage-dependence of its amplitude did not resemble the action of
NMDA on neocortical neurons.