Heptanol but not fluoroacetate prevents the propagation of spreading depression in rat hippocampal slices. Carlota Largo, Geoffrey C. Tombaugh, Peter G. Aitken, Oscar Herreras and George G. Somjen. Depto de Investigaci[acute]on, Hospital Ram[acute]on y Cajal, 28034 Madrid, Spain, Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
APStracts 3:0215N, 1996.
We investigated whether heptanol and other long-chain alcohols that are known to block gap junctions interfere with the generation or the propagation of spreading depression (SD). Waves of SD were triggered by micro-injection of concentrated KCl solution in stratum (st.) radiatum of CA1 of rat hippocampal tissue slices. DC-coupled recordings of extracellular potential (V o ) were made at the injection site and at a second site approximately 1 mm distant in st. radiatum and sometimes also in st. pyramidale. Extracellular excitatory postsynaptic potentials (fEPSPs) were evoked by stimulation of the Schaffer collateral bundle; in some experiments antidromic population spikes were evoked by stimulation of the alveus. Bath application of 3 mM heptanol or 5 mM hexanol completely and reversibly prevented the propagation of the SD-related potential shift (_V o ) without abolishing the _V o at the injection site. Octanol (1 mM) had a similar but less reliably reversible effect. fEPSPs were depressed by about 30% by heptanol and octanol, 65% by hexanol. Antidromic population spikes were depressed by 30%. In isolated, patch-clamped CA1 pyramidal neurons heptanol partially and reversibly depressed voltage- dependent Na + currents possibly explaining the slight depression of antidromic spikes and, by acting on presynaptic action potentials, also the depression of fEPSPs. Fluoroacetate (FAc), a putative selective blocker of glial metabolism, first induced multiple spike firing in response to single afferent volleys and then severely suppressed synaptic transmission (confirming earlier reports), without depressing the antidromic population spike. FAc did not inhibit SD propagation. The effect of alkyl alcohols is compatible with the idea that the opening of normally closed neuronal gap junctions is required for SD propagation. Alternative possible explanations include interference with the lipid phase of neuron membranes. The absence of SD inhibition by FAc confirms that synaptic transmission is not necessary for the propagation of SD, and it suggest that normally functioning glial cells are not essential for SD generation or propagation.

Received 15 March 1996; accepted in final form 10 September 1996.
APS Manuscript Number J218-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996