Journal of Neuroscience, Vol 8, 4589-4602, Copyright © 1988 by Society for Neuroscience
Evidence that guanosine triphosphate (GTP)-binding proteins control a synaptic response in brain: effect of pertussis toxin and GTP gamma S on the late inhibitory postsynaptic potential of hippocampal CA3 neurons
RH Thalmann
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
These experiments show that a synaptic response in brain, namely, the late
inhibitory postsynaptic potential (IPSP) of hippocampal CA3 neurons in the
rat hippocampal slice, was blocked by 2 compounds affecting guanosine
triphosphate (GTP)-binding proteins. The first of these compounds,
pertussis toxin, an inactivator of several GTP-binding proteins
(G-proteins), excluding the GTP-binding protein that stimulates adenylyl
cyclase, was injected intrahippocampally. The second compound, GTP gamma S,
a nonhydrolyzable analog of GTP, was injected directly into postsynaptic
neurons via the recording electrode. An ADP-ribosylation assay verified
that the pertussis toxin had modified a major portion of the hippocampal
pertussis toxin substrates of approximately 40,000 apparent molecular
weight. Each agent blocked the conductance associated with both the late
IPSP and the response to baclofen, an agonist for a putative receptor
mediating the late IPSP (GABAB). These compounds did not block the mossy
fiber excitatory postsynaptic potential (EPSP), the GABAA-mediated early
IPSP, or the response to the GABAA agonist 4,5,6,7-tetrahydroisoxazolo-
(5,4-C)-pyridin-3-ol. It is possible that these measurements underestimated
the degree of blockade of the specific potassium conductance of the late
IPSP since at least a portion of the GTP-gamma S-insensitive response was
not a potassium conductance at all. Rather, it was a response with a
reversal potential some 30 mV positive to that of the late IPSP. On the
basis of these experiments, I propose that the transmitter receptor of the
late IPSP activates a potassium conductance via a G-protein that is
sensitive to blockade by pertussis toxin and that GTP gamma S and baclofen
activate a conductance that depends upon the same G-proteins and/or
potassium channels as does the late IPSP.