Hay M, Hoang C J, Pamidimukkala J
Dalton Cardiovascular Research Center, Department of Veterinary Biomedical Sciences, University of Missouri, Research Park, Columbia, MO 65251, USA.
Ann N Y Acad Sci. 2001 Jun;940:119-31. doi: 10.1111/j.1749-6632.2001.tb03671.x.
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.
本章的目的是回顾在理解参与动脉压力感受器神经传递调节的细胞和生物物理机制方面的一些最新进展。体内和体外实验均已表明，在中枢压力感受器突触处，重复神经元刺激后会出现突触抑制或疲劳。由于大多数中枢神经元的囊泡数量有限，因此胞吐作用后囊泡的回收或内吞作用被认为在维持突触传递中起主要作用。我们推测，中枢压力感受器终末可能通过对突触前代谢型谷氨酸受体（mGluRs）的反馈激活来抑制其自身的突触传递。我们使用标准膜片钳技术分析了mGluR自身受体（III组mGluRs）对电压门控钙通道的影响，并使用定量成像染料FM1-43和FM2-10分析了其对主动脉压力感受器神经元胞吐和内吞过程的影响。使用全细胞膜片钳技术，我们发现用L-AP4激活III组mGluRs可抑制钙通道电流峰值。此外，用L-AP4激活III组mGluRs可显著降低主动脉压力感受器神经元中由刺激诱导的胞吐作用（用FM1-43测量），并抑制突触结合蛋白I的磷酸化。这些结果表明，激活III组mGluRs可能通过以下方式抑制突触传递：（1）抑制钙内流；（2）减少突触囊泡胞吐；（3）调节控制突触囊泡回收和内吞的机制。mGluRs对压力感受器突触囊泡的这些作用可能导致体内观察到的压力感受器/孤束核突触抑制。
