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Journal of Neuroscience, Vol 6, 782-789, Copyright © 1986 by Society for Neuroscience
Decline in calcium cooperativity as the basis of facilitation at the squid giant synapse
EF Stanley
The role of Ca in transmitter release and facilitation has been examined at
the squid giant synapse by evaluating the effect of changes in the external
concentration of Ca on the excitatory postsynaptic potential (EPSP).
Changes in Ca were achieved by means of an arterial perfusion technique,
circumventing the diffusion barrier that exists between the synapse and the
bathing medium. Transmitter release was found to follow a high power (n) of
the external Ca at low nonsaturating Ca concentrations and low stimulus
frequencies: 4.0 +/- 0.1 (mean +/- SE) in 22 experiments. The value of n
was not fixed, however, but declined at stimulus frequencies above 0.3 Hz
to 2.9 at Hz, 2.3 at 10 Hz, 1.7 at 50 Hz, and 1.1 at 80 Hz. This decline in
n was due to a greater proportional facilitation of the EPSP at lower Ca
levels. In a separate experiment, facilitation was determined at a fixed
low Ca level over a wide range of stimulus frequencies. A plot of the
maximum percentage increase in the EPSP against the stimulus frequency
described three "steps," with plateaus occurring at 0.3-10 Hz, 10-50 Hz,
and over 80 Hz. The timing of these steps corresponds to the stimulus
frequencies at which the cooperativity declines. The results of this study
indicate that the cooperative action of four Ca ions are required to
trigger the transmitter release mechanism, and that the phenomenon of
facilitation involves a reduction in Ca cooperativity. It is proposed that
Ca ions can bind up to four receptors on the release site and that binding
results in the opening of "gates." The opening of all four gates triggers
transmitter release.(ABSTRACT TRUNCATED AT 250 WORDS)
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