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  • Title: Nonhydrolyzable analogues of GTP activate a new Na+ current in a rat mast cell line.
    Author: Parekh AB.
    Journal: J Biol Chem; 1996 Sep 20; 271(38):23161-8. PubMed ID: 8798510.
    Abstract:
    Whole-cell patch clamp experiments were performed to examine the effects of the nonhydrolyzable GTP analogue, guanosine 5'-3-O-(thio)triphosphate, on membrane currents in rat basophilic leukemia cells. Guanosine 5'-3-O-(thio)triphosphate activated an inward sodium current. This current had a new permeability sequence to monovalent cations and a different pharmacological profile to that of other characterized Na+ channels. Long hyperpolarizing steps revealed that the current declined during the pulse, and the decline was voltage-dependent. Activation of the current required Mg2+ and ATP. The nonhydrolyzable ATP analogues, adenosine 5'-O-(thio)triphosphate and adenosine 5'-(beta,gamma-imino)triphosphate, could not substitute for ATP. Soluble second messengers like 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 certain nonexcitable cells.
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