Tetrabutylammonium: a selective blocker of the somatostatin-activated hyperpolarizing current in mouse AtT-20 corticotrophs.
To obtain a clearer understanding of the mechanisms by which somatostatin modulates stimulus-secretion coupling in neuroendocrine cells, we investigated the pharmacology of the somatostatin-activated inward rectifier in mouse pituitary tumour cells (AtT-20 corticotrophs). Individual AtT-20 cells displayed spontaneous, long-lasting action potentials that caused transient spikes in cytosolic [Ca2+] ([Ca]i). Application of 1-10 nM somatostatin led to membrane hyperpolarization and loss of [Ca]i spiking activity. Voltage-clamp recordings revealed that the somatostatin-induced hyperpolarization was due to an inwardly rectifying K+ current. Tetrabutyl-ammonium (TBA+) inhibited both outward and inward currents through the inward rectifier, whereas Cs+ blocked only inward current and tetraethylammonium (TEA+) was completely ineffective in blocking somatostatin-activated currents. However TEA+, but neither TBA+ nor Cs+, blocked voltage-gated outward currents. Correspondingly, TBA+ abolished the hyperpolarizing effects of somatostatin and, of the three K+ channel blockers, only TBA+ prevented the somatostatin-induced inhibition of [Ca]i spiking. TBA+ may thus prove a useful tool in elucidating the underlying mechanisms by which somatostatin affects the secretory activity of neuroendocrine cells.
Thomas
P
P
Department of Pharmacology, University of Cambridge, United Kingdom. pjt28@cam.ac.uk
Smith
P A
PA
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002586:Cesium / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology*; D051379:Mice; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010911:Pituitary Neoplasms; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D013004:Somatostatin / Q000494:pharmacology*; D019789:Tetraethylammonium / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology
D003902:Detergents; D006728:Hormones; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; D002586:Cesium; D013004:Somatostatin; D019789:Tetraethylammonium; D000324:Adrenocorticotropic Hormone; C009405:tetrabutylammonium; D011188:Potassium; D002118:Calcium