Quantitative properties and receptor reserve of the IP3 and calcium branch of Gq-coupled receptor signaling

Eamonn J Dickson, Björn H. Falkenburger, Bertil Hille

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Gq-coupled plasma membrane receptors activate phospholipase C (PLC), which hydrolyzes membrane phosphatidylinositol 4,5-bisphosphate (PIP2) into the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). This leads to calcium release, protein kinase C (PKC) activation, and sometimes PIP2 depletion. To understand mechanisms governing these diverging signals and to determine which of these signals is responsible for the inhibition of KCNQ2/3 (KV7.2/7.3) potassium channels, we monitored levels of PIP2, IP3, and calcium in single living cells. DAG and PKC are monitored in our companion paper(Falkenburger et al. 2013. J. Gen. Physiol. http://dx.doi.org/10.1085/jgp.201210887). Theresults extend our previous kinetic model of Gq-coupled receptor signaling to IP3 and calcium. We find that activation of low-abundance endogenous P2Y2 receptors by a saturating concentration of uridine 5'-triphosphate (UTP; 100 μM) leads to calcium release but not to PIP2 depletion. Activation of overexpressed M1 muscarinic receptors by 10 μM Oxo-M leads to a similar calcium release but also depletes PIP2. KCNQ2/3 channels are inhibited by Oxo-M (by 85%), but not by UTP (<1%). These differences can be attributed purely todifferences in receptor abundance. Full amplitude calcium responses can be elicited even after PIP2 was partially depleted by overexpressed inducible phosphatidylinositol 5-phosphatases, suggesting that very low amounts of IP3 suffice to elicit a full calcium release.Hence, weak PLC activation can elicit robust calcium signals without net PIP2 depletion or KCNQ2/3 channel inhibition.

Original languageEnglish (US)
Pages (from-to)521-535
Number of pages15
JournalJournal of General Physiology
Volume141
Issue number5
DOIs
StatePublished - May 2013
Externally publishedYes

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Calcium-Sensing Receptors
Inositol 1,4,5-Trisphosphate Receptors
Calcium
Uridine Triphosphate
Type C Phospholipases
Phosphatidylinositols
Protein Kinase C
KCNQ2 Potassium Channel
Purinergic P2Y2 Receptors
Diacylglycerol Kinase
Muscarinic M1 Receptors
Inositol 1,4,5-Trisphosphate
Diglycerides
Second Messenger Systems
Phosphoric Monoester Hydrolases
Cell Membrane
Membranes

ASJC Scopus subject areas

  • Physiology

Cite this

Quantitative properties and receptor reserve of the IP3 and calcium branch of Gq-coupled receptor signaling. / Dickson, Eamonn J; Falkenburger, Björn H.; Hille, Bertil.

In: Journal of General Physiology, Vol. 141, No. 5, 05.2013, p. 521-535.

Research output: Contribution to journalArticle

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