Cellular mechanisms regulating synaptic vesicle exocytosis and endocytosis in aortic baroreceptor neurons.
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 neurotransmission. 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.
Hay
M
M
Dalton Cardiovascular Research Center, Department of Veterinary Biomedical Sciences, University of Missouri, Research Park, Columbia, MO 65251, USA. haym@missouri.edu
Hoang
C J
CJ
Pamidimukkala
J
J
D000818:Animals; D001011:Aorta / Q000294:innervation*; D004705:Endocytosis / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D011311:Pressoreceptors / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology*