BACKGROUND & AIMS: Because of their diffuse distribution, neuroendocrine cells of the gut have not been isolated successfully for electrophysiological characterization. We therefore established primary cell cultures from surgically resected human carcinoids and investigated them electrophysiologically. METHODS: The neuroendocrine identity of the isolated gut tumor cells was determined immunocytochemically. The electrophysiological properties of the cells were studied by the patch-clamp technique. RESULTS: The primary cell cultures expressed neurofilament proteins, cytokeratins, and key proteins of the secretion machinery. Spontaneous action potentials were observed in most cells. Using the whole-cell mode of the patch-clamp technique, tetrodotoxin-sensitive voltage-gated sodium currents as well as voltage-gated calcium currents were identified. Calcium channel currents were carried mainly by dihydropyridine-sensitive, L-type calcium channels. The L-type calcium channel currents were also partially blocked by the omega-conotoxins GVIA and MVIIC. Moreover, omega-agatoxin IVA reversibly reduced a component of the calcium channel currents, indicating that neuroendocrine gut tumor cells express different types of voltage-gated calcium channels. In addition, somatostatin was found to inhibit partially the voltage-dependent calcium channel currents and thus calcium-dependent hormone release. CONCLUSIONS: Carcinoid cells of the human gut are electrically excitable cells. They express voltage-dependent sodium and calcium channels as well as somatostatin receptors.
BACKGROUND & AIMS: Because of their diffuse distribution, neuroendocrine cells of the gut have not been isolated successfully for electrophysiological characterization. We therefore established primary cell cultures from surgically resected human carcinoids and investigated them electrophysiologically. METHODS: The neuroendocrine identity of the isolated gut tumor cells was determined immunocytochemically. The electrophysiological properties of the cells were studied by the patch-clamp technique. RESULTS: The primary cell cultures expressed neurofilament proteins, cytokeratins, and key proteins of the secretion machinery. Spontaneous action potentials were observed in most cells. Using the whole-cell mode of the patch-clamp technique, tetrodotoxin-sensitive voltage-gated sodium currents as well as voltage-gated calcium currents were identified. Calcium channel currents were carried mainly by dihydropyridine-sensitive, L-type calcium channels. The L-type calcium channel currents were also partially blocked by the omega-conotoxins GVIA and MVIIC. Moreover, omega-agatoxin IVA reversibly reduced a component of the calcium channel currents, indicating that neuroendocrine gut tumor cells express different types of voltage-gated calcium channels. In addition, somatostatin was found to inhibit partially the voltage-dependent calcium channel currents and thus calcium-dependent hormone release. CONCLUSIONS: Carcinoid cells of the human gut are electrically excitable cells. They express voltage-dependent sodium and calcium channels as well as somatostatin receptors.
Authors: L Kölby; P Bernhardt; H Ahlman; B Wängberg; V Johanson; A Wigander; E Forssell-Aronsson; S Karlsson; B Ahrén; G Stenman; O Nilsson Journal: Am J Pathol Date: 2001-02 Impact factor: 4.307