Somatostatin release, electrical activity, membrane currents and exocytosis in human pancreatic delta cells
Somatostatin release, electrical activity, membrane currents and exocytosis in human pancreatic delta cells
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DOI：
10.1007/s00125-009-1382-z
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发表时间：
2009-08-01
期刊：
影响因子：
8.2
通讯作者：
Rorsman, P.
中科院分区：
文献类型：
--
作者：
Braun, M.;Ramracheya, R.;Rorsman, P.
本研究的目的是表征人类三角洲细胞/胰岛的电活动、离子通道、胞吐和生长抑素释放。葡萄糖刺激的生长抑素释放从完整的人胰岛测量。用免疫细胞化学方法记录了个体δ细胞的膜电位、电流和膜电容的变化（反映胞吐）。葡萄糖和甲磺丁酰胺刺激人胰岛生长抑素分泌，二氮氧化合物抑制生长抑素分泌。人δ细胞产生突发性或零星的电活动，甲磺丁酰胺增强了这种活动，但葡萄糖不受影响。Delta细胞含有对甲苯丁酰胺不敏感、对Ba2+敏感的内整流K+电流和两种电压门控的K+电流，对四乙基铵/基质毒素（延迟整流，Kv2.1/2.2）和4-氨基吡啶（a电流）敏感。电压门控河豚毒素（TTX）敏感的Na+电流有助于动作电位上升，但TTX对生长抑素释放没有影响。δ细胞具有被isradipine (L)、omega-agatoxin （P/Q）和NNC 55-0396 (T)阻断的Ca2+通道。阻断这些通道中的任何一条都会干扰δ细胞的电活动，并消除葡萄糖刺激的生长抑素释放。电容测量揭示了对ω -agatoxin敏感的去极化诱发的胞吐的缓慢组分。动作电位放电是由atp敏感的K+通道活动调节的。膜电位由Ba2+敏感的内整流K+通道稳定。电压门控的L型和t型Ca2+通道是电活动所必需的，而Na+电流和P/ q型Ca2+通道有助于（但不是必需的）动作电位的上升。动作电位复极由a型通道和Kv2.1/2.2 K+通道介导。胞吐作用通过P/ q型Ca2+通道与Ca2+内流密切相关。葡萄糖刺激生长抑素分泌涉及K-ATP通道依赖性和非依赖性过程。
The aim of this study was to characterise electrical activity, ion channels, exocytosis and somatostatin release in human delta cells/pancreatic islets.Glucose-stimulated somatostatin release was measured from intact human islets. Membrane potential, currents and changes in membrane capacitance (reflecting exocytosis) were recorded from individual human delta cells identified by immunocytochemistry.Somatostatin secretion from human islets was stimulated by glucose and tolbutamide and inhibited by diazoxide. Human delta cells generated bursting or sporadic electrical activity, which was enhanced by tolbutamide but unaffected by glucose. Delta cells contained a tolbutamide-insensitive, Ba2+-sensitive inwardly rectifying K+ current and two types of voltage-gated K+ currents, sensitive to tetraethylammonium/stromatoxin (delayed rectifying, Kv2.1/2.2) and 4-aminopyridine (A current). Voltage-gated tetrodotoxin (TTX)-sensitive Na+ currents contributed to the action potential upstroke but TTX had no effect on somatostatin release. Delta cells are equipped with Ca2+ channels blocked by isradipine (L), omega-agatoxin (P/Q) and NNC 55-0396 (T). Blockade of any of these channels interferes with delta cell electrical activity and abolishes glucose-stimulated somatostatin release. Capacitance measurements revealed a slow component of depolarisation-evoked exocytosis sensitive to omega-agatoxin.Action potential firing in delta cells is modulated by ATP-sensitive K+-channel activity. The membrane potential is stabilised by Ba2+-sensitive inwardly rectifying K+ channels. Voltage-gated L- and T-type Ca2+ channels are required for electrical activity, whereas Na+ currents and P/Q-type Ca2+ channels contribute to (but are not necessary for) the upstroke of the action potential. Action potential repolarisation is mediated by A-type and Kv2.1/2.2 K+ channels. Exocytosis is tightly linked to Ca2+-influx via P/Q-type Ca2+ channels. Glucose stimulation of somatostatin secretion involves both K-ATP channel-dependent and -independent processes.