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This Article Full Text Full Text (PDF) All Versions of this Article: 549/1/157    most recent 2002.034439v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tosetti, P. Articles by Toselli, M. Search for Related Content PubMed PubMed Citation Articles by Tosetti, P. Articles by Toselli, M.

Chick RGS2L demonstrates concentration-dependent selectivity for pertussis toxin-sensitive and -insensitive pathways that inhibit L-type Ca²⁺ channels

Patrizia Tosetti, Valeria Parente*, Vanni Taglietti*, Kathleen Dunlap and Mauro Toselli*

In neuronal cells, the influx of Ca²⁺ ions through voltage-dependent L-type calcium (L) channels couples excitation to multiple cellular functions. In addition to voltage, several neurotransmitters, hormones and cytokines regulate L channel gating via binding to G-protein-coupled receptors. Intracellular molecules that modify G-protein activity - such as regulator of G-protein-signalling (RGS) proteins - are therefore potential candidates for regulating Ca²⁺ influx through L channels. Here we show that a novel RGS2 splice variant from chick dorsal root ganglion (DRG) neurons, RGS2L, reduces bradykinin (BK)-mediated inhibition of neuronal L channels and accelerates recovery from inhibition. Chick RGS2 reduces the inhibition mediated by both the pertussis toxin (PTX)-sensitive (G_i/o-coupled) and the PTX-insensitive (presumably G_q/11-coupled) pathways. However, we demonstrate for the first time in a living cell that the extent of coupling to each pathway varies with RGS2L concentration. A low concentration of recombinant chick RGS2L (10 nM) preferentially reduces the inhibition mediated by the PTX-insensitive pathway, whereas a 100-fold higher concentration attenuates both PTX-sensitive- and PTX-insensitive-mediated components equally. Our data suggest that factors promoting RGS2L gene induction may regulate Ca²⁺ influx through L channels by recruiting low-affinity interactions with G_i/o that are absent at basal RGS2L levels.