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De Vuyst E, Boengler K, Antoons G, et al. Pharmacological modulation of connexin-formed channels in cardiac pathophysiology. Br J Pharmacol. 2011;163(3):469-83doi: 10.1111/j.1476-5381.2011.01244.x.
De Vuyst, E., Boengler, K., Antoons, G., Sipido, K. R., Schulz, R., & Leybaert, L. (2011). Pharmacological modulation of connexin-formed channels in cardiac pathophysiology. British journal of pharmacology, 163(3), 469-83. https://doi.org/10.1111/j.1476-5381.2011.01244.x
De Vuyst, Elke, et al. "Pharmacological modulation of connexin-formed channels in cardiac pathophysiology." British journal of pharmacology vol. 163,3 (2011): 469-83. doi: https://doi.org/10.1111/j.1476-5381.2011.01244.x
De Vuyst E, Boengler K, Antoons G, Sipido KR, Schulz R, Leybaert L. Pharmacological modulation of connexin-formed channels in cardiac pathophysiology. Br J Pharmacol. 2011 Jun;163(3):469-83. doi: 10.1111/j.1476-5381.2011.01244.x. PMID: 21265827; PMCID: PMC3101610.
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Br J Pharmacol. 2011 Jun;163(3):469-83. doi: 10.1111/j.1476-5381.2011.01244.x.

Pharmacological modulation of connexin-formed channels in cardiac pathophysiology.

British journal of pharmacology

Elke De Vuyst, Kerstin Boengler, Gudrun Antoons, Karin R Sipido, Rainer Schulz, Luc Leybaert

Affiliations

  1. Department of Basic Medical Sciences - Physiology group, Faculty of Medicine and Health Sciences, Ghent University, Belgium.

PMID: 21265827 PMCID: PMC3101610 DOI: 10.1111/j.1476-5381.2011.01244.x

Abstract

Coordinated electrical activity in the heart is supported by gap junction channels located at the intercalated discs of cardiomyocytes. Impaired gap junctional communication between neighbouring cardiomyocytes contributes to the development of re-entry arrhythmias after myocardial ischaemia. Current antiarrhythmic therapy is hampered by a lack of efficiency and side effects, creating the need for a new generation of drugs. In this review, we focus on compounds that increase gap junctional communication, thereby increasing the conduction velocity and decreasing the risk of arrhythmias. Some of these compounds also inhibit connexin 43 (Cx43) hemichannels, thereby limiting adenosine triphosphate loss and volume overload following ischaemia/reperfusion, thus potentially increasing the survival of cardiomyocytes. The compounds discussed in this review are: (i) antiarrythmic peptide (AAP), AAP10, ZP123; (ii) GAP-134; (iii) RXP-E; and (vi) the Cx mimetic peptides Gap 26 and Gap 27. None of these compounds have effects on Na(+) , Ca(2+) and K(+) channels, and therefore have no proarrhythmic activity associated with currently available antiarrhythmic drugs. GAP-134, RXP-E, Gap 26 and Gap 27 are pharmalogical agents with a favorable clinical safety profile, as already confirmed in phase I clinical trials for GAP-134. These agents show an excellent promise for treatment of arrhythmias in patients with ischaemic cardiomyopathy.

© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

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