INVOLVEMENT OF A GARDOS-TYPE POTASSIUM CHANNEL IN HEAD ACTIVATOR-INDUCED MITOSIS OF BON CELLS

The human neuroendocrine cell line BON was used to study second messen gers involved in signal transduction for entry into mitosis. BON cells produce the neuropeptide head activator (HA) and use it as autocrine growth factor. HA stimulates BON cell proliferation by triggering entr y into mitosis. HA-induced mitosis is mediated by an inhibitory G prot ein, the action of which is blocked by pertussis toxin. HA signaling r equires inhibition of the cAMP pathway, calcium influx, and hyperpolar ization of cells. The latter is a very important and sensitive step in volving a calcium-activated potassium channel. Cell cycle progression and proliferation of BON cells are most efficiently inhibited with spe cific inhibitors of this potassium channel. Pharmacology and RNA analy sis suggest identity with the recently cloned Gardos-type potassium ch annel.