Spreading depression induced by 100 mM KCl in caudate is blocked by local anesthesia of the substantia nigra

Abstract

Pressure-ejection of 100 mM KCl was used to induce voltammetric signals in the rat caudate. The signals, detected chronoamperometrically with Nafion-coated carbon fiber microelectrodes, were reproducibly generated at 20-min intervals up to distances of 1600 μm from the KCl stimulus site. Unilateral 6-hydroxydopamine lesions of the substantia nigra (SN) demonstrated that over 90% of the voltammetric signal generated was dopamine. Evaluation of the signal onset at two widely spaced electrodes suggested that injection of nl volumes of 100 mM KCl into the rat caudate generates voltammetric signals which resemble spreading depression (SD) produced by more classical methods (e.g. 1 M KCl). We further investigated this phenomenon by simultaneous evaluation of extracellular K + ion concentration changes, field potential (FP) and voltammetric signals or multiunit activity following stimulation with 100 mM or 1 M KCl. The results show that the signals generated by 100 mM KCl have many of the attributes of ‘classical’ SD, although the extracellular K + ion concentration changes and FP changes were smaller in magnitude. However, the characteristic burst of multiunit activity followed by a marked quiescent period found during 1 M KCl stimulation was not observed with 100 mM KCl stimulation. Furthermore, application of 0.5% lidocaine to the SN reversibly blocked all signals generated by 100 mM KCl in the caudate while similar treatment with up to 2% lidocaine was ineffective when 1 M KCl was used as the stimulus. The results suggest that the signals generated by 100 mM KCl may represent an attenuated form of SD which requires a functioning SN, and that this stimulation could be a useful model for studying neurotransmitter interactions in the propagation of the SD phenomena.