In:
The Journal of Physiology, Wiley, Vol. 549, No. 1 ( 2003-05), p. 157-169
Abstract:
In neuronal cells, the influx of Ca 2+ 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 Ca 2+ 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 n m ) 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 Ca 2+ influx through L channels by recruiting low‐affinity interactions with G i/o that are absent at basal RGS2L levels.
Type of Medium:
Online Resource
ISSN:
0022-3751
,
1469-7793
DOI:
10.1113/jphysiol.2002.034439
Language:
English
Publisher:
Wiley
Publication Date:
2003
detail.hit.zdb_id:
1475290-6
SSG:
12
