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J Mol Cell Cardiol. 2006 Jul;41(1):17-25. Epub 2006 May 30.

Alpha1-adrenergic receptor signaling is localized to caveolae in neonatal rat cardiomyocytes.

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Cellular Biochemistry Laboratory, Baker Heart Research Institute, PO Box 6492 St. Kilda Road Central, Melbourne, 8008 Victoria, Australia.


In neonatal rat cardiomyocytes, phosphatidylinositol(4,5)bisphosphate (PIP2) is a precursor of second messengers, a stabilizer of ion channels and exchangers, an anchor point for the cytoskeleton and, in addition, can serve as a signaling molecule in its own right. We examined the possibility that sarcolemmal PIP2 exists in different pools and that only one of these provides the substrate for alpha1-adrenergic receptor activated phospholipase C (PLC). Membranes were separated on the basis of buoyant density, and the light lipid raft fractions were further separated into caveolae and non-caveolar rafts using immunoprecipitation. PIP2 was principally located in the light lipid raft fractions and was equally distributed between caveolae and non-caveolar membranes. Heavier membrane fractions also contained some PIP2. Addition of the alpha1-adrenergic receptor agonist phenylephrine (50 microM) caused reductions in PIP2, but only in caveolae. PIP2 in other fractions was unaffected. In agreement with this, PLCbeta1 and, to a lesser extent, Galphaq were concentrated in this fraction. PLCbeta3 was primarily observed in heavier membranes. We conclude that PIP2 in cardiomyocyte sarcolemma is compartmentalized and that alpha1-adrenergic receptor signaling is localized to caveolae.

[Indexed for MEDLINE]

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