G(i)-dependent localization of β2-adrenergic receptor signaling to L-type Ca2+ channels

Ye Chen-Izu, Rui Ping Xiao, Leighton T Izu, Heping Cheng, Meike Kuschel, Harold Spurgeon, Edward G. Lakatta

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

A plausible determinant of the specificity of receptor signaling is the cellular compartment over which the signal is broadcast. In rat heart, stimulation of β1-adrenergic receptor (β1-AR), coupled to G(s)-protein, or β2-AR, coupled to G(s)- and G(i)-proteins, both increase L-type Ca2+ current, causing enhanced contractile strength. But only β1-AR stimulation increases the phosphorylation of phospholamban, troponin-I, and C-protein, causing accelerated muscle relaxation and reduced myofilament sensitivity to Ca2+. β2-AR stimulation does not affect any of these intracellular proteins. We hypothesized that β2-AR signaling might be localized to the cell membrane. Thus we examined the spatial range and characteristics of β1-AR and β2-AR signaling on their common effector, L-type Ca2+ channels. Using the cell-attached patch-clamp technique, we show that stimulation of β1-AR or β2-AR in the patch membrane, by adding agonist into patch pipette, both activated the channels in the patch. But when the agonist was applied to the membrane outside the patch pipette, only β1-AR stimulation activated the channels. Thus, β1-AR signaling to the channels is diffusive through cytosol, whereas β2-AR signaling is localized to the cell membrane. Furthermore, activation of G(i) is essential to the localization of β2-AR signaling because in pertussis toxin-treated cells, β2-AR signaling becomes diffusive. Our results suggest that the dual coupling of β2-AR to both G(s)- and G(i)-proteins leads to a highly localized β2-AR signaling pathway to modulate sarcolemmal L-type Ca2+ channels in rat ventricular myocytes.

Original languageEnglish (US)
Pages (from-to)2547-2556
Number of pages10
JournalBiophysical Journal
Volume79
Issue number5
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics

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  • Cite this

    Chen-Izu, Y., Xiao, R. P., Izu, L. T., Cheng, H., Kuschel, M., Spurgeon, H., & Lakatta, E. G. (2000). G(i)-dependent localization of β2-adrenergic receptor signaling to L-type Ca2+ channels. Biophysical Journal, 79(5), 2547-2556.