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