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This Article Full Text Full Text (PDF) All Versions of this Article: 293/5/H3056    most recent 00515.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shen, J.-B. Articles by Liang, B. T. Search for Related Content PubMed PubMed Citation Articles by Shen, J.-B. Articles by Liang, B. T.

Characterization and mechanism of P2X receptor-mediated increase in cardiac myocyte contractility

¹Pat and Jim Calhoun Cardiology Center and ²Department of Pharmacology, University of Connecticut Health Center, Farmington, Connecticut

Submitted 30 April 2007 ; accepted in final form 29 August 2007

Cardiac P2X purinergic receptors can mediate an increase in myocyte contractility and a potentially important role in the heart. The P2X₄ receptor (P2X₄R) is an important subunit of native cardiac P2X receptors. With transgenic mice with cardiac-specific overexpression of P2X₄R (Tg) used as a model, the objectives here were to characterize the P2X receptor-mediated cellular contractile and Ca²⁺ transient effects and to determine the mechanism underlying the receptor-induced increase in myocyte contractility. In response to the agonist 2-methylthioATP (2-meSATP), Tg myocytes showed an increased intracellular Ca²⁺ transient, as defined by fura 2 fluorescence ratio, and an enhanced contraction shortening that were unaccompanied by cAMP accumulation or L-type Ca²⁺ channel activation. The increased Ca²⁺ transient was not associated with any alteration in action potential duration, resting membrane potential, or diastolic fluorescence ratio or rates of rise and decline of the Ca²⁺ transient. Simultaneous Ca²⁺ transient and contraction measurements did not show any agonist-mediated change in myofilament Ca²⁺ sensitivity. However, activation of the overexpressed P2X₄ receptor caused an enhanced SR Ca²⁺ loading, as evidenced by a 2-meSATP-evoked increase in the caffeine-induced inward current and Ca²⁺ transient. Similar data were obtained in wild-type mouse ventricular myocytes. Thus an increased SR Ca²⁺ content, occurring in the absence of cAMP accumulation or L-type Ca²⁺ channel activation, is the principal mechanism by which cardiac P2X receptor mediates a stimulatory effect on cardiac myocyte contractility.

purines; calcium; sarcoplasmic reticulum