HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Matkovich, S. J. Articles by Woodcock, E. A. Search for Related Content PubMed PubMed Citation Articles by Matkovich, S. J. Articles by Woodcock, E. A. Social Bookmarking                      What's this?

J Biol Chem, Vol. 275, Issue 15, 10845-10850, April 14, 2000

Ca²⁺-activated but Not G Protein-mediated Inositol Phosphate Responses in Rat Neonatal Cardiomyocytes Involve Inositol 1,4,5-Trisphosphate Generation^*

Scot J. Matkovich and Elizabeth A. Woodcock

From the Cellular Biochemistry Laboratory, Baker Medical Research Institute, Melbourne 8008, Victoria, Australia

Inositol phosphate (InsP) responses to receptor activation are assumed to involve phospholipase C cleavage of phosphatidylinositol 4,5-bisphosphate to generate Ins(1,4,5)P₃. However, in [³H]inositol-labeled rat neonatal cardiomyocytes (NCM) both initial and sustained [³H]InsP responses to ₁-adrenergic receptor stimulation with norepinephrine (100 µM) were insensitive to the phosphatidylinositol 4,5-bisphosphate-binding agent neomycin (5 mM). Introduction of 300 µM unlabeled Ins(1,4,5)P₃ into guanosine 5'-3-O-(thio)triphosphate (GTPS)-stimulated, permeabilized [³H]inositol-labeled NCM increased [³H]Ins(1,4,5)P₃ slightly but did not significantly reduce levels of its metabolites [³H]Ins(1,4)P₂ and [³H]Ins(4)P, suggesting that these [³H]InsPs are not formed principally from [³H]Ins(1,4,5)P₃. In contrast, the calcium ionophore A23187 (10 µM) provoked [³H]InsP responses in intact NCM which were sensitive to neomycin, and elevation of free calcium in permeabilized NCM led to [³H]InsP responses characterized by marked increases in [³H]Ins(1,4,5)P₃ (2.9 ± 0.2% of total [³H]InsPs after 20 min of high Ca²⁺ treatment in comparison to 0.21 ± 0.05% of total [³H]InsPs accumulated after 20 min of GTPS stimulation). These data provide evidence that Ins(1,4,5)P₃ generation is not a major contributor to G protein-coupled InsP responses in NCM, but that substantial Ins(1,4,5)P₃ generation occurs under conditions of Ca²⁺ overload. Thus in NCM, Ca²⁺-induced Ins(1,4,5)P₃ generation has the potential to worsen Ca²⁺ overload and thereby aggravate Ca²⁺-induced electrophysiological perturbations.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				N. N Petrashevskaya, I. Bodi, S. E Koch, S. A Akhter, and A. Schwartz Effects of {alpha}1-adrenergic stimulation on normal and hypertrophied mouse hearts. Relation to caveolin-3 expression Cardiovasc Res, August 15, 2004; 63(3): 561 - 572. [Abstract] [Full Text] [PDF]

				E. A. Woodcock, B. H. Wang, J. F. Arthur, A. Lennard, S. J. Matkovich, X.-J. Du, J. H. Brown, and R. D. Hannan Inositol Polyphosphate 1-Phosphatase Is a Novel Antihypertrophic Factor J. Biol. Chem., June 14, 2002; 277(25): 22734 - 22742. [Abstract] [Full Text] [PDF]

				J. F. Arthur, S. J. Matkovich, C. J. Mitchell, T. J. Biden, and E. A. Woodcock Evidence for Selective Coupling of alpha 1-Adrenergic Receptors to Phospholipase C-beta 1 in Rat Neonatal Cardiomyocytes J. Biol. Chem., September 28, 2001; 276(40): 37341 - 37346. [Abstract] [Full Text] [PDF]