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. Tetrabutylammonium (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 TBA(+), 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.