Heptanol but not fluoroacetate prevents the propagation of spreading
depression in rat hippocampal slices.
Largo, Carlota, 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 3:0202N, 1996.
1. We investigated whether heptanol and related compounds interfere with the
generation or the propagation of spreading depression (SD). These compounds
are known to block gap junctions. 2. Waves of SD were triggered by micro-
injection of concentrated KCl solution in stratum (st.) radiatum of CA1 region
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. 3. 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 and antidromic population spikes were
depressed by about 30% by heptanol and octanol, 65% by hexanol. 4. In
isolated, patch-clamped CA1 pyramidal neurons heptanol partially and
reversibly depressed voltage-dependent Na + currents. This can explain the
slight depression of antidromic spikes and, by acting on presynaptic action
potentials, also the depression of fEPSPs. 5. These results are compatible
with the idea that the opening of normally closed neuronal gap junctions are
required for SD propagation. Alternative possible explanations include
interference with the lipid phase of neuron membranes. 6. Fluoroacetate, 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. Fluoroacetate did not inhibit SD propagation.
These results confirm that synaptic transmission is not necessary for the
generation or the propagation of SD, and 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 7 October 1996