Ammori John B, Zhang Weizhen, Newman Erika A, Mulholland Michael W
Department of Surgery, The University of Michigan Medical Center, 2101 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-0346, USA.
J Gastrointest Surg. 2007 Aug;11(8):1016-24. doi: 10.1007/s11605-007-0176-1.
The dorsal motor nucleus of the vagus (DMNV) integrates peripheral and central signals and sends efferent output to the gastrointestinal system. Glutamate, the major excitatory neurotransmitter of the central nervous system, causes increases in intracellular calcium in DMNV neurons. The mechanisms by which glutamate activates calcium signaling in the DMNV were examined. DMNV neurons were isolated from neonatal rat brainstem using microdissection and enzymatic digestion. Exposure to glutamate caused intracellular Ca(2+) increments in greater than 80% of cells. Removal of extracellular Ca(2+) abolished intracellular Ca(2+) transients. Kynurenic acid, a nonspecific glutamate receptor antagonist, abolished intracellular Ca(2+) transients. Exposure to glutamate while blocking AMPA receptors with GYKI 52466 abolished the Ca(2+) response. Exposure to (S)AMPA, an AMPA receptor agonist, caused intracellular Ca(2+) increments in 97% of cells. Activation and antagonism of NMDA and kainate receptors produced no changes compared to control experiments. NiCl, a nonspecific Ca(2+) channel blocker, abolished intracellular Ca(2+) transients. Blocking T-type Ca(2+) channels with mibefradil abolished the Ca(2+) response in 76% of cells. Blockade of L-type and N-type Ca(2+) channels did not affect the Ca(2+) response. Glutamate mediates intracellular Ca(2+) currents in DMNV neurons via the AMPA receptor and T-type Ca(2+) channels, allowing influx of extracellular Ca(2+).
迷走神经背核(DMNV)整合外周和中枢信号,并向胃肠系统发送传出输出。谷氨酸是中枢神经系统的主要兴奋性神经递质,可导致DMNV神经元内的细胞内钙增加。研究了谷氨酸在DMNV中激活钙信号传导的机制。使用显微解剖和酶消化从新生大鼠脑干中分离出DMNV神经元。暴露于谷氨酸会导致超过80%的细胞内Ca(2+)增加。去除细胞外Ca(2+)可消除细胞内Ca(2+)瞬变。犬尿氨酸是一种非特异性谷氨酸受体拮抗剂,可消除细胞内Ca(2+)瞬变。在用GYKI 52466阻断AMPA受体的同时暴露于谷氨酸可消除Ca(2+)反应。暴露于AMPA受体激动剂(S)AMPA会导致97%的细胞内Ca(2+)增加。与对照实验相比,NMDA和海人藻酸受体的激活和拮抗作用没有产生变化。非特异性Ca(2+)通道阻滞剂NiCl可消除细胞内Ca(2+)瞬变。用米贝地尔阻断T型Ca(2+)通道可消除76%的细胞中的Ca(2+)反应。阻断L型和N型Ca(2+)通道不影响Ca(2+)反应。谷氨酸通过AMPA受体和T型Ca(2+)通道介导DMNV神经元中的细胞内Ca(2+)电流,使细胞外Ca(2+)流入。