G(i)-dependent localization of beta(2)-adrenergic receptor signaling to L-type Ca(2+)channels

Citation
Ci. Ye et al., G(i)-dependent localization of beta(2)-adrenergic receptor signaling to L-type Ca(2+)channels, BIOPHYS J, 79(5), 2000, pp. 2547-2556
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOPHYSICAL JOURNAL
ISSN journal
0006-3495 → ACNP
Volume
79
Issue
5
Year of publication
2000
Pages
2547 - 2556
Database
ISI
SICI code
0006-3495(200011)79:5<2547:GLOBRS>2.0.ZU;2-F
Abstract
A plausible determinant of the specificity of receptor signaling is the cel lular compartment over which the signal is broadcast. In rat heart, stimula tion of beta (1)-adrenergic receptor (beta (1)-AR), coupled to G(s)-protein , or beta (2)-AR, coupled to G(s)- and G(i)-proteins, both increase L-type Ca2+ current, causing enhanced contractile strength. But only beta (1)-AR s timulation increases the phosphorylation of phospholamban, troponin-l, and C-protein, causing accelerated muscle relaxation and reduced myofilament se nsitivity to Ca2+. beta (2)-AR stimulation does not affect any of these int racellular proteins. We hypothesized that beta (2)-AR signaling might be lo calized to the cell membrane. Thus we examined the spatial range and charac teristics of beta (1)-AR and beta (2)-AR signaling on their common effector , L-type Ca2+ channels. Using the cell-attached patch-clamp technique, we s how that stimulation of beta (1)-AR or beta (2)-AR in the patch membrane, b y adding agonist into patch pipette, both activated the channels in the pat ch. But when the agonist was applied to the membrane outside the patch pipe tte, only beta (1)-AR stimulation activated the channels. Thus, beta (1)-AR signaling to the channels is diffusive through cytosol, whereas beta (2)-A R signaling is localized to the cell membrane. Furthermore, activation of G i is essential to the localization of beta (2)-AR signaling because in pert ussis toxin-treated cells, beta (2)-AR signaling becomes diffusive. Our res ults suggest that the dual coupling of beta (2)-AR to both G(s)- and G(i)-p roteins leads to a highly localized beta (2)-AR signaling pathway to modula te sarcolemmal L-type Ca2+ channels in rat ventricular myocytes.