Editorial Cardiac gap junctions : good or bad ? *

See article by Yasui et al. [30] (pp. 68 –76) in this stimulus, inducing apoptosis in this model as well as the issue. exact mechanism of protection remain unclear. Yasui et al. [30] suggest that a dilution of apoptosis-inducing factors Gap junctions enable the cytoplasm of individual cells to through gap junctions into adjacent cells may explain the communicate directly and allow exchange of nutrients, protective effect. But the protection may also be due to ions, metabolites and small molecules up to about 1000 Da propagation of signals inhibiting apoptosis. Factors de[1]. Connexins, which are coded for by a multigene family, scribed as apoptosis inhibiting in heart like Bcl-2 or FGF are the subunits of gap junctions. In adult mammalian [8,9] are too large to pass through gap junctions. And it myocardium four different connexins, connexin43 (Cx43), will be of great interest to further characterize the mechaCx40, Cx45 and Cx37, have been identified [2]. In nism of protection and especially to identify the molecule 1 / 2 heterozygous Cx43 mice connexin43 has been shown that passes through gap junctions. The model described in to be the main conductor of intercellular current in the the study of Yasui et al. may become a useful tool to ventricle [3]. The gap junctions are mainly localized at the identify apoptosis associated signals exchanged between intercalated discs of the cardiomyocytes [4]. cells which either promote or inhibit apoptosis in adjacent Although all these details on structure and function of cells. single gap junctions are known, their importance for heart The findings of Yasui et al. [30] may be surprising, since function is a matter of ongoing investigations. Best studied in other cell types an enhancement of cell–cell coupling is their role in synchronization of electrical activation and through gap junctions has usually been found to increase 21 contraction of cardiac myocytes [5]. Gap junctional uncouthe number of apoptotic cells, e.g., after Ca -overload, pling is associated with electrical instability and appearoxidative stress or metabolic inhibition [10]. However, ance of arrhythmias [6]. On the other hand gap junctional when comparing the results two specific aspects of the communication seems to play a role in the development of study of Yasui et al. [30] should be considered: first, in this manifest myocardial cell injury. It has recently been shown study no single, defined stimulus for apoptosis induction that gap junctional uncoupling can limit infarct size in the was added to the cells. Second, the authors are looking at a heart [7]. If gap junctions are also involved in apoptotic process that takes several days until apoptosis appears, cardiac cell death has remained an open question. The whereas in other studies apoptosis was induced within 24 study of Yasui et al. [30] in this issue is indeed the first h. Although under these specific conditions gap junctions report that examines the influence of gap junctional prevent apoptosis induction, the study does not exclude communication on induction of apoptosis in carthat under different conditions apoptosis might be propdiomyocytes. They show in neonatal cardiomyocyte culagated via gap junctions to adjacent cells in the heart. tures that inhibition of Cx43 synthesis by antisense oligoFactors that are known to induce apoptosis in carnucleotides results in a decreased coupling of myocytes diomyocytes, like calcium [11], cAMP [12] or cGMP [13], and in an increased number of apoptotic cells. The are able to pass through gap junctions [14] and may therefore induce apoptosis in neighboring healthy cells. But many of these inducers are also known to close gap *Tel.: 149-641-994-7246; fax: 149-641-994-7239. junctions [15,16] and may therefore prevent transduction E-mail address: [email protected] (G. Taimor). of death signals between cells.