Electrical prodromals of spreading depression void Grafstein’s potassium hypothesis

Open Access
Publisher Website
Google Scholar
Abstract
Since Leao’s initial description (Leão 1944), a confusion too often found in the literature is to assume that the mechanism of SD movement can be grasped by looking into its main phase. However, it has long been established that SD is a complex chain of tightly bound events (Marshall 1959) with different thresholds, which may share or not share their macroscopic, cellular, and subcellular mechanisms. The advancing front and the main phase can be dissociated in several ways (see e.g., Herreras and Somjen 1993a). Also, many authors reported “patches” of depression that remained motionless in the elicitation locus (e.g., Largo et al. 1997). In Grafstein’s hypothesis, intense neuron firing, potassium elevation, and excitation of nearby neurons constitute the crucial cycle of events for SD movement and also accounted for the subsequent major neuron depolarization. Its long-standing success must be credited to the early finding of the associated interstitial potassium flood, which conditioned the interpretation of subsequent findings, and to the simplicity of these biophysical relations: an excitatory extracellular moraine fed by the neurons themselves (the same principle underlies the glutamate hypothesis; see Van Harreveld 1959). A number of results, scarcely mentioned in the literature, undermine the potassium hypothesis. We enlist here only a few: 1) tetrodotoxin blockade of neuron firing causes no change to SD, and thus neuron firing is not required (Sugaya et al. 1975). 2) Voltage clamping does not avoid SD-related membrane conductance (Czéh et al. 1993); initial excitation is thus not a requisite (see Somjen et al. 1991). 3) SDs may change into spreading convulsions moving at the same speed (Van Harreveld and Stamm 1953), which differentiates spreading and inactivating mechanisms. 4) Potassium and DC voltage signals follow a similar temporal course but opposite changes in magnitude (Herreras and Somjen 1993b). 5) Our latest most surprising finding shows that neurons undergo longitudinal gradients of depolarization, which are explained by the zonal dendritic opening of a large ion conductance, new equilibrium potentials, and axial currents (Canals et al. 2004), not potassium levels.

This publication has 21 references indexed in Scilit: