The effect of barbiturate and procaine in glial and neuronal contributions to evoked cortical steady potential shifts

The negative steady potential (SP) shift associated with the direct cortical response (evoked by slow repetitive stimulation) is believed to be generated by glial depolarization secondary to a transient increase in [K⁺]₀. This SP shift is augmented by barbiturate and reduced by procaine. To elucidate these drug effects the direct cortical response was studied simultaneously with intracellular recording from glia in one group of experiments and with measurements of [K⁺₀ in another. Barbiturate produced the expected increase in the negative SP shift, but had either no effect, or slightly reduced glial slow depolarization (SD). The effect on [K⁺_o was similar. These findings argue against glial SD as being the only source of the SP shift during barbiturate anesthesia and suggest a significant neuronal contribution. That this is so is strongly suggested by finding a reversal in polarity of the barbiturate augmented negative SP shift, 600-900 μm below the cortical surface. This reversal is expected for a potential generated by vertically oriented neurons and differs from the situation before barbiturate administration when the SP shift does not reverse but becomes progressively smaller in the cortical depth, consistent with a glial origin for the SP shift.

With procaine, the SP shift and SD are modified similarly. They both undergo a quantitatively appropriate amplitude reduction. The effect of procaine on [K⁺₀ could not be tested since procaine directly effects ion-sensitive K⁺ electrodes. Laminar analysis of the reduced negative SP shift after procaine is qualitatively similar to the finding before giving the drug; there is no reversal. We believe the reduced SP shift after procaine continues to reflect glial SD. Procaine can diminish both direct and synaptic neural excitation which would result in a smaller extracellular liberation of K⁺ and hence a smaller glial SD and SP shift. By contrast, barbiturate which can also depress synaptic excitation is believed, in addition, to uncover and enhance (especially by prolongation) postsynaptic inhibition. Thus, after barbiturate, the augmented SP shift may reflect the addition of two separately generated surface negatives-glial SD and summated hyperpolarizing IPSPs in cortical depth. © 1977.