The Journal of Neuroscience, July 15, 1998, 18(14):5160-5169
Neuromodulators Enhance Transmitter Release by Two Separate
Mechanisms at the Inhibitor of Crayfish Opener Muscle
Andrey
Vyshedskiy1,
Kerry R.
Delaney2, and
Jen-Wei
Lin1
1 Department of Biology, Boston University, Boston,
Massachusetts 02215, and 2 Department of Biological
Sciences, Simon Fraser University, Burnaby, British Columbia, V5A 156 Canada
A presynaptic voltage control method has been used to investigate
the modulatory effects of serotonin (5-HT) and okadaic acid (OA) on the
inhibitory junction of the crayfish opener muscle. Instead of using
action potentials, we used 20 msec pulses depolarized to 0 mV to
activate transmitter release. This approach allowed us to monitor two
separate physiological parameters related to the release process. The
first parameter, transmitter release kinetics, is characterized as the
delay when inhibitory postsynaptic conductance reaches its half-maximum
(IPSG50). The second parameter, the total area of
IPSG (IPSGarea), estimates total transmitter output.
We have reported previously that the F2 component of synaptic facilitation is associated with a decrease in IPSG50 but
without a change in IPSGarea. These results raised the
possibility that IPSG50 and IPSGarea could be
mediated by separate mechanisms that were modulated independently. To
explore this possibility, we investigated the effects of 5-HT (100-200
nM) and OA (2.5 µM) on the two parameters.
5-HT and OA enhanced IPSG neither by changing the sensitivity of
postsynaptic receptors, as tested by iontophoretically ejected GABA,
nor by elevating resting and action potential-activated presynaptic
free calcium, as monitored by fura-2 imaging. 5-HT and OA decreased
IPSG50 by 3.0 ± 1.4 and 3.6 ± 1.1 msec,
respectively, and increased IPSGarea by 50 ± 21 and
37 ± 6%, respectively. The ability of F2 facilitation to
accelerate release kinetics was reduced in the presence of the
modulators, suggesting that the mechanism underlying the accelerated
release kinetics was shared by the two modes of synaptic enhancement.
This report demonstrates that the acceleration in release kinetics and
the increase in total release are two separate mechanisms for enhancing
transmitter output and that these two mechanisms can be activated
without changes in presynaptic calcium dynamics.
Key words:
IPSG; GABA; synaptic transmission; modulators; transmitter release; serotonin; okadaic acid
Copyright © 1998 Society for Neuroscience 0270-6474/98/18145160-10$05.00/0