ELECTROPHYSIOLOGICAL PROPERTIES OF HUMAN CARCINOID CELLS OF THE GUT

Background & Aims: Because of their diffuse distribution, neuroendocri ne cells of the gut have not been isolated successfully for electrophy siological characterization. We therefore established primary cell cul tures from surgically resected human carcinoids and investigated them electrophysiologically. Methods: The neuroendocrine identity of the is olated gut tumor cells was determined immunocytochemically. The electr ophysiological 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 w hole-cell mode of the patch-clamp technique, tetrodotoxin-sensitive vo ltage-gated sodium currents as well as voltage-gated calcium currents were identified. Calcium channel currents were carried mainly by dihyd ropyridine-sensitive, L-type calcium channels. The L-type calcium chan nel 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 t umor cells express different types of voltage-gated calcium channels. In addition, somatostatin was found to inhibit partially the voltage-d ependent calcium channel currents and thus calcium-dependent hormone r elease. Conclusions: Carcinoid cells of the human gut are electrically excitable cells. They express voltage-dependent sodium and calcium ch annels as well as somatostatin receptors.