Nonhydrolyzable analogues of GTP activate a new Na+ current in a rat mast cell line.
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.
Parekh
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Max-Planck-Institute for Biophysical Chemistry, Postfach 2841, Am Fassberg, Göttingen D-37077, Germany.
D000818:Animals; D001692:Biological Transport; D002463:Cell Membrane Permeability; D016764:Cell Polarity; D004553:Electric Conductivity; D005459:Fluorides / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives*; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism; D006868:Hydrolysis; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D015290:Second Messenger Systems; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D013873:Thionucleotides / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015222:Sodium Channels; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D006165:Guanylyl Imidodiphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C023427:guanosine 5'-O-(2-thiodiphosphate); D006160:Guanosine Triphosphate; D012964:Sodium; D005459:Fluorides