Redistribution of connexin43 in regional acute ischemic myocardium: influence of ischemic preconditioning

1 Zentrum Anaesthesiologie, Abteilung Anaesthesiologische Forschung, and 2 Zentrum Anatomie, Abteilung Elektronenmikroskopie, Universität Göttingen, Göttingen, Germany Submitted 7 November 2005 ; accepted in final form 9 March 2006 Connexins are known to play an essential role in the ischemic preconditioning (IP) of the heart; their functional role in this process, however, has not been clearly defined. For this reason, anesthetized rats were subjected to regional myocardial ischemia, with or without IP or reperfusion. In frozen sections of hearts, fluorescence immunohistochemical staining for connexin43 (Cx43) was performed. In contrast to undisturbed zones, tissue that had been subjected to ischemia revealed Cx43 immunostaining not only in the gap junctions but also in a conspicuous pattern in the free cellular membranes of the myocytes. In myocardium that was exposed to IP only, the ratio of immunofluorescence intensity in the free cellular membrane to that in the interior of the cell was 1.22 ± 0.04 (ratio in non-ischemia-exposed area = 1.04 ± 0.01). When 15 or 45 min of permanent ischemia followed IP, the effect became more evident (ratio = 1.31 ± 0.03 and 1.46 ± 0.03, respectively) and proved to be significantly greater than in the corresponding non-IP groups (ratio = 1.16 ± 0.03 and 1.30 ± 0.03, respectively, P < 0.01). Reperfusion led to an overall weakening of fluorescence intensities and a disappearance of the observed IP-specific differences. We conclude that IP initiates a redistribution of Cx43 from its natural position in the gap junctions toward the free plasma membrane, thereby improving the cell's chance of survival during the subsequent phase of prolonged ischemia by an unknown, supposedly gap junction-independent, mechanism. gap junctions; immunohistochemistry; nonjunctional connexin Address for reprint requests and other correspondence: F. Vetterlein, Abteilung Anaesthesiologische Forschung, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany (e-mail: fvetterl{at}med.uni-goettingen.de )