NONHYDROLYZABLE ANALOGS OF GTP ACTIVATE A NEW NA-CELL LINE( CURRENT IN A RAT MAST)

Whole cell patch clamp experiments were performed to examine the effec ts of the nonhydrolyzable GTP analogue, guanosine 5'-3-O-(thio)triphos phate, on membrane currents in rat basophilic leukemia cells, Guanosin e 5'-3-O-(thio)triphosphate activated an inward sodium current, This c urrent had a new permeability sequence to monovalent cations and a dif ferent pharmacological profile to that of other characterized Na+ chan nels. Long hyperpolarizing steps revealed that the current declined du ring the pulse, and the decline was voltage-dependent. Activation of t he current required Mg2+ and ATP. The nonhydrolyzable ATP analogues, a denosine 5'-O-(thio)triphosphate and adenosine 5'-(beta,gamma-imino)tr iphosphate, could not substitute for ATP, Soluble second messengers li ke cAMP, cGMP, inositol polyphosphates, and Ca2+ did not activate the Na+ current, These results suggest that nonhydrolyzable GTP analogues activate a Na+ current in rat basophilic leukemia cells that is new in terms of its selectivity, pharmacology, and activation mechanism. It may be the prototype for a new family of Na+ channels expressed in cer tain nonexcitable cells.