SOMATOSTATIN STIMULATES CA2+-ACTIVATED K+ CHANNELS THROUGH PROTEIN DEPHOSPHORYLATION

THE neuropeptide somatostatin inhibits secretion from electrically excitable cells in the pituitary, pancreas, gut and brain 1. In mammalian pituitary tumour cells somatostatin inhibits secretion through two distinct pertussis toxin-sensitive mechanisms 2-5. One involves inhibition of adenylyl cyclase 6, the other an unidentified cyclic AMP-independent mechanism that reduces Ca2+ influx 7,8 by increasing membrane conductance to potassium 9,10. Here we demonstrate that the predominant electrophysiological effect of somatostatin on metabolically intact pituitary tumour cells is a large, sustained increase in the activity of the large-conductance Ca2+- and voltage-activated K+ channels (BK). This action of somatostatin does not involve direct effects of Ca2+, cAMP or G proteins on the channels. Our results indicate instead that somatostatin stimulates BK channel activity through protein dephosphorylation.