Dalton Cardiovascular Research Center, Department of Veterinary Biomedical Sciences, University of Missouri, Columbia, Missouri 65251, USA
Address for correspondence: Meredith Hay, Ph.D., Dalton Cardiovascular Research Center, Research Park, University of Missouri, Columbia, MO 65251. Voice: 573-882-0044; fax: 573-884-4232.
haym{at}missouri.edu
The purpose of this chapter is to review some of the recent
progress in the understanding of the cellular and biophysical
mechanisms that are involved in the regulation of arterial baroreceptor
neurotransmssion. Synaptic depression or fatigue following repeated
neuronal stimulation has been shown at central baroreceptor
synapses
in vivo and
in vitro. As most of the central neurons
have a limited number of vesicles, vesicle retrieval or endocytosis
following exocytosis is thought to play a major role in preserving
synaptic transmission. We have hypothesized that central baroreceptor
terminals may inhibit their own synaptic transmission via feedback
activation of presynaptic metabotropic glutamate receptors (mGluRs).
We have analyzed the effects of mGluR autoreceptors (group III
mGluRs) on voltage-gated calcium channels using standard patch-clamp
techniques and on the process of exocytosis and endocytosis
in aortic baroreceptor neurons using the quantitative imaging
dye FM1-43 and FM2-10. Usng the whole-cell patch-clamp technique,
we have found that activation of group III mGluRs with L-AP4
inhibits peak calcium channel current. Furthermore, activation
of group III mGluRs with L-AP4 markedly decreases stimulation-induced
exocytosis in aortic baroreceptor neurons, as measured with
FM1-43, and inhibits synapsin I phosphorylation. These results
suggest that activation of group III mGluRs may inhibit synaptic
transmission by (1) inhibiting calcium influx, (2) decreasing
synaptic vesicle exocytosis, and (3) modulating the mechanisms
governing synaptic vesicle recovery and endocytosis. These effects
of mGluRs on baroreceptor synaptic vesicles may contribute to
the baroreceptor/nucleus tractus solitarius synaptic depression
observed
in vivo.
