On the Action of the Anti-Absence Drug Ethosuximide in the Rat and Cat Thalamus

ETX decreases the sustained outward whole-cell current in TC neurons. A₁, Whole-cell currents show the reversible reduction by ETX (0.25 mm) of the sustained current in a TC neuron of the rat LGN.A₂, Steady-state current–voltage plot for the same neuron as in A₁ (theinset is an enlargement of the region around the action potential threshold). B₁, Whole-cell current reduction by ETX (0.5 mm).B₂, Steady-state current–voltage plot for the same neuron as in B₁ (theinset is an enlargement of the region around the action potential threshold). C₁, In a rat TC neuron recorded in a low Ca²⁺ (0.5 mm) and high Mg²⁺ (8 mm) medium, ETX (0.5 mm) had no effect on the sustained current.C₂, Steady-state current–voltage plot for the same neuron as in C₁.

Lack of action of ETX on voltage-activated Ca²⁺ currents. A, Whole-cell currents show no difference between control and ETX (0.75 mm) in the amplitude and kinetics of I_T in TC neurons of VB slices (see Materials and Methods for details of voltage protocols). B, Normalized steady-state activation and inactivation curves show no effect of ETX (0.75 mm) on the voltage dependence of I_T measured in six TC neurons from rat VB slices (see Results for further details).C–F, Each trace (average of five records) is the maximal IT recorded in the different neurons indicated and shows the lack of action of ETX (0.75 mm) on the amplitude and kinetics of the current (for all traces the holding potential was −110 mV, and the voltage command was 60 mV). Only the records inD were obtained from dissociated neurons.G, Single traces show the lack of action of ETX (1 mm) in a TC neuron of the rat LGN on the high-threshold Ca²⁺ current. Subsequent application of (±)-baclofen (50 μm) in the continuing presence of ETX produced a clear reduction of the peak amplitude. These data were used to construct the plot of the peak amplitude of the high-threshold Ca²⁺ current versus time (on theright), which clearly shows the wash-out of the current, the lack of action of ETX, and the reduction by (±)-baclofen. Note how the run-down of the current is abolished in the presence of (±)-baclofen (cf. Guyon and Leresche, 1995).

ETX increases the apparent input resistance of TC neurons in cat and rat LGN slices at potentials greater than −60 mV.A₁,B₁, Families of voltage responses and input currents recorded in the absence and in the presence of ETX, using sharp electrode recordings. The records inB₁ were obtained in the presence of 1 μm TTX. A₂,B₂, Voltage–current plots (from the same neurons as in A₁ andB₁, respectively) show an increase in the apparent input resistance at potentials greater than −60 mV during perfusion of the slice with ETX. Each point is the average of three measurements. The resting membrane potential is −60 mV in A₁ andB₁.

ETX increases tonic firing of TC neurons in slices. A, Depolarizing voltage pulses show an increased tonic firing in the presence of ETX (0.5 mm) for similar values of injected currents (records from a cat LGN neuron). The action potential height is truncated. B, Plots of firing frequency versus injected current (from the data in A) show a decreased firing frequency at the third (and higher) interspike intervals (ISI) in the presence of ETX (0.5 mm) for input currents of 0.3–0.35 nA. C, At lower input currents (0.2–0.4 nA) the number of action potentials evoked by a pulse of 1.5 sec duration is increased in the presence of ETX (0.5 mm) (from the data in A).

ETX decreases burst firing of TC neurons in rat and cat LGN slices. A, Burst firing produced by LTCPs evoked after a 2-sec-long voltage deflection (amplitude as indicated) in the presence and absence of ETX. Note the loss of one action potential and the increased latency of the burst in the presence of ETX (0.5 mm). B, Plot of latency of the first action potential in the burst (calculated from the end of the 2-sec-long voltage response) versus the amplitude of the preceding voltage deflection indicates a clearly increased latency in the case of the smallest voltage responses (data from the cat LGN neuron inA). C, The burst-firing frequency achieved at the interspike intervals (ISI) indicated is plotted against the amplitude of the voltage deflection preceding the LTCP. Note the decrease in the maximal firing frequency achieved at almost all ISI and the loss of one or two action potentials observed in the presence of ETX (top plots are from a TC neuron in the rat LGN; bottom plots are from a TC neuron in the cat LGN).