Department of Cell and Systems Physiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu 807-8555, Japan.
Department of Cell and Systems Physiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu 807-8555, Japan.
Auton Neurosci. 2023 Sep;248:103108. doi: 10.1016/j.autneu.2023.103108. Epub 2023 Jul 10.
One of the mechanisms for hypertension is an increase in blood catecholamines due to increased secretion from sympathetic nerve terminals and adrenal medullary chromaffin (AMC) cells. Spontaneously hypertensive rats (SHRs) are used as an animal model of hypertension. Catecholamine secretion in AMC cells occurs in response to humoral factors and neuronal inputs from the sympathetic nerve fibres. Acetylcholine (ACh) released from the nerve terminals activates nicotinic as well as muscarinic ACh receptors. The present experiment aimed to elucidate whether muscarinic receptor-mediated excitation is altered in SHR AMC cells and, if it is, how. Compared with normotensive rat AMC cells, muscarinic stimulation induced greater catecholamine secretion and larger depolarising inward currents in SHR AMC cells. In contrast to normotensive rat AMC cells, the muscarine-induced current consisted of quinine-sensitive and quinine-insensitive components. The former and the latter are possibly ascribed to nonselective cation channel activation and TWIK-related acid-sensitive K (TASK) channel inhibition, as noted in guinea pig AMC cells. In fact, immunoreactive material for TASK1 and several isoforms of transient receptor potential canonical (TRPC) channels was detected in SHR AMC cells. Stromal interaction molecule 1 (STIM1), which plays an essential role for heteromeric TRPC1-TRPC4 channel formation and is not expressed in normotensive rat AMC cells, was detected in the cytoplasm and co-localised with TRPC1. The expression of muscarinic M receptors was enhanced in SHR AMC cells compared with normotensive rats. The results indicate that muscarinic excitation is enhanced in SHR AMC cells, probably through facilitation of TRPC channel signalling.
高血压的机制之一是由于交感神经末梢和肾上腺髓质嗜铬细胞（AMC）分泌增加，血液儿茶酚胺增加。自发性高血压大鼠（SHR）被用作高血压动物模型。AMC 细胞中的儿茶酚胺分泌是对体液因子和来自交感神经纤维的神经元输入的反应。从神经末梢释放的乙酰胆碱（ACh）激活烟碱型和毒蕈碱型 ACh 受体。本实验旨在阐明 SHR AMC 细胞中是否改变了毒蕈碱受体介导的兴奋，如果改变了，是如何改变的。与正常血压大鼠 AMC 细胞相比，毒蕈碱刺激在 SHR AMC 细胞中诱导更大的儿茶酚胺分泌和更大的去极化内向电流。与正常血压大鼠 AMC 细胞不同，毒蕈碱诱导的电流由奎尼丁敏感和奎尼丁不敏感成分组成。前者和后者可能归因于非选择性阳离子通道激活和 TWIK 相关酸敏感 K（TASK）通道抑制，如在豚鼠 AMC 细胞中所注意到的。事实上，在 SHR AMC 细胞中检测到 TASK1 和几种瞬时受体电位经典（TRPC）通道同工型的免疫反应性物质。基质相互作用分子 1（STIM1）在异源 TRPC1-TRPC4 通道形成中起重要作用，并且在正常血压大鼠 AMC 细胞中不表达，在细胞质中被检测到，并与 TRPC1 共定位。与正常血压大鼠相比，SHR AMC 细胞中毒蕈碱 M 受体的表达增强。结果表明，SHR AMC 细胞中的毒蕈碱兴奋增强，可能通过促进 TRPC 通道信号转导。
