Dr. Axel Radlach Pries,
The session gave a very broad and lively overview of different new and relevant aspects of connexin function in cardiovascular biology. It was opened by a presentation by HVM Van Rijen (Utrecht, NL) on the ‘The role of connexins in arrhythmias’. As an introduction, he gave an overview on gap junctional communication and expression of different connexins in the heart. With respect to the topic of arrhythmia, the most relevant connexin seems to be CX43. Next, he introduced the concept of arrythmogenic requirements, concluding that the central hypothesis is linked to the propagation wavelength, which is given as the velocity of the propagation times the duration of the refractive period.
While connexins would play a central role for the propagation properties, he did report experimental results in mice, suggesting that a reduction of CX43 expression alone did not really lead to an arrythmogenic phenotype. Next he eluded to the involvement of Na+-currents and the fibre content in the tissue. All three parameters (CX43 deficiency, reduced Na+-channel density and increased fibre content) alone could not provoke an arrythmogenic phenotype. The same was true mostly for combinations of two factors. Only all three together would result in reduced propagation speed and arrhythmic events, providing evidence for the robustness of anti-arrythmic mechanisms in the heart.
The next two presentations by B R Kwak (Geneva, CH) and K Boengler (Essen, DE) highlighted the involvement of connexins in atherosclerosis and in preconditioning. BR Kwak demonstrated that in atherosclerotic lesions, the connexin pattern is substantially altered relative to healthy endothelium. In her talk, she developed the hypothesis that this changed pattern is pro-atherosclerotic due to the increased attraction of mononuclear leucocytes. In this process, the generation of intraluminal Adenosine by the molecule CD73 plays a central role. The presentation of K Boengler focused on the specific role of CX 43 in the inner membrane of sub-sarcolemmal mitochondria. They are involved in the release of reactive oxygen species (ROS) which, in turn, are involved in preconditioning.
In the final presentation C De Wit (Luebeck, DE) elegantly showed the implication of ‘Connexins in hypertension’.For the control of blood pressure and the development of hypertension, the role of the connexins in the vessel wall, especially of resistance arteries and arterioles, but also in the kidney has to be considered. In his studies, combining intravital microscopy with histological techniques, he showed that a CX40 knockout leads to increased blood pressure and reduced conduction along the arteriolar vessel wall. It also impairs the increase of renal renin production in response to increasing blood pressure. The latter effect seems to be the strongest cause for the increased blood pressure. Also, he showed that for this renal function but not for arteriolar function, CX 45 can replace CX 40.
Taken together, these presentations have shown how relevant and fast the progress in the analysis of connexin function in the heart and the vasculature has been recently. Certainly there is much more to expect!
Connexins: old proteins with new functions
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