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) All Versions of this Article: 295/5/H2106    most recent 00456.2008v1 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Totzeck, A. Articles by Schulz, R. Search for Related Content PubMed PubMed Citation Articles by Totzeck, A. Articles by Schulz, R.

No impact of protein phosphatases on connexin 43 phosphorylation in ischemic preconditioning

¹Institut für Pathophysiologie, Universitätsklinikum Essen, Essen, Germany; and ²Servicio de Cardiologia, Hospital Vall d'Hebron, Barcelona, Spain

Submitted 30 April 2008 ; accepted in final form 26 September 2008

Cardiac connexin 43 (Cx43) is involved in infarct propagation, and the uncoupling of Cx43-formed channels reduces infarct size. Cx43-formed channels open upon Cx43 dephosphorylation, and ischemic preconditioning (IP) prevents the ischemia-induced Cx43 dephosphorylation. In addition to the sarcolemma, Cx43 is also present in the cardiomyocyte mitochondria. We now examined the interaction of Cx43 with protein phosphatases PP1, PP2A, and PP2B and the role of such interaction for Cx43 phosphorylation in preconditioned myocardium. Infarct size (in %area at risk) in left ventricular anterior myocardium of Göttinger minipigs subjected to 90 min of low-flow ischemia and 120 min of reperfusion was 23.1 ± 2.7 [n = 7, nonpreconditioned (NIP) group] and was reduced by IP to 10.0 ± 3.2 (n = 6, P < 0.05). Mitochondrial and gap junctional Cx43 dephosphorylation increased after 85 min of ischemia in NIP myocardium, whereas Cx43 phosphorylation was preserved with IP. PP2A and PP1, but not PP2B, were detected by Western blot analysis in the left ventricular myocardium. Cx43 coprecipitated with PP2A but not with PP1. Although the total PP2A immunoreactivity (confocal laser scan) was increased to 154 ± 24% and 194 ± 13% of baseline (P < 0.05) after 85 min of ischemia in NIP and IP myocardium, respectively, the PP2A activities were similar between the groups. The amount of PP2A coimmunoprecipitated with Cx43 remained unchanged. Only PP2A coprecipitates with Cx43 in pig myocardium. This interaction is not affected by IP, suggesting that PP2A is not involved in the prevention of the ischemia-induced Cx43 dephosphorylation by IP.

cardioprotection; ischemia-reperfusion