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: 293/3/H1714    most recent 00022.2007v1 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 HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Shintani-Ishida, K. Articles by Yoshida, K.-i. Search for Related Content PubMed PubMed Citation Articles by Shintani-Ishida, K. Articles by Yoshida, K.-i.

Hemichannels in cardiomyocytes open transiently during ischemia and contribute to reperfusion injury following brief ischemia

Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

Submitted 6 January 2007 ; accepted in final form 6 June 2007

The aim of this study was to investigate changes in hemichannel activity during in vitro simulated ischemia [oxygen-glucose deprivation (OGD)] and the contribution of hemichannels to ischemia-reperfusion injury in rat neonatal cardiomyocytes. Dye uptake assays showed that hemichannels opened as OGD progressed, peaking after 1 h, and then closed, returning to the pre-OGD state after 2 h of OGD. The increase in dye uptake after 1 h of OGD was inhibited by hemichannel blockers (lanthanum chloride and a connexin 43 mimetic peptide, Gap26). During OGD, intracellular Ca²⁺ concentration ([Ca²⁺]_i) began to increase after 1 h and reached several micromolar after 2 h. After 1 h of OGD, Gap26 inhibited the increases in hemichannel activity and [Ca²⁺]_i. In contrast, dantrolene [an endo(sarco)plasmic reticulum Ca²⁺ release inhibitor] suppressed the increase in [Ca²⁺]_i, but not in hemichannel activity. After 2 h of OGD, the combined administration of 2',4'-dichlorobenzamil and dantrolene reduced [Ca²⁺]_i to <1 µM and increased hemichannel activity to the level attained after 1 h of OGD. Simulated ischemia-reperfusion, induced by 1 h of OGD followed by 2 h of recovery, reduced cell viability to 54% of the control level. The addition of Gap26 to OGD medium improved viability to 80% of the control level. In conclusion, this study demonstrated that 1) hemichannels open transiently during OGD, 2) closure of hemichannels, but not their opening, is regulated by an increase in [Ca²⁺]_i during OGD, and 3) open hemichannels contribute to cell injury during recovery from OGD.

gap junction; connexin; ischemia-reperfusion

This article has been cited by other articles:

				M. Ruiz-Meana, A. Rodriguez-Sinovas, A. Cabestrero, K. Boengler, G. Heusch, and D. Garcia-Dorado Mitochondrial connexin43 as a new player in the pathophysiology of myocardial ischaemia-reperfusion injury Cardiovasc Res, January 15, 2008; 77(2): 325 - 333. [Abstract] [Full Text] [PDF]