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Am J Physiol Heart Circ Physiol 291: H357-H367, 2006. First published January 20, 2006; doi:10.1152/ajpheart.00681.2005
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Analysis of effects of connexin-mimetic peptides in rat mesenteric small arteries

Vladimir V. Matchkov,1 Awahan Rahman,1 Linda M. Bakker,2 Tudor M. Griffith,2 Holger Nilsson,1 and Christian Aalkjær1

1The Water and Salt Research Center, Institute of Physiology and Biophysics, University of Aarhus, Aarhus, Denmark; 2Department of Diagnostic Radiology, Wales Heart Research Institute, Cardiff University, Cardiff, United Kingdom

Submitted 22 June 2005 ; accepted in final form 13 January 2006

Synthetic peptides homologous to the extracellular loops of the major vascular connexins represent a novel class of gap junction blockers that have been used to assess the role of direct cellular communication in arteries and veins. However, the specificity of action of such peptides on the coupling between smooth muscle cells (SMCs) has not yet been fully characterized. Isolated third-order rat mesenteric arteries were therefore studied with respect to isometric tension (myography), intracellular Ca2+ concentraton ([Ca2+]i) (Ca2+-sensitive dyes), membrane potential, and input resistance (sharp intracellular glass electrodes). Confocal imaging was used for visualization of [Ca2+]i events in individual SMCs in the arterial wall and membrane currents (patch clamp) measured in individual SMCs isolated from the same arteries. A triple peptide combination (37,43Gap 27 + 40Gap 27 + 43Gap 26) increased intercellular resistance (measured as input resistance) in intact arterial segments without affecting the membrane conductance of individual cells and also interrupted electrical coupling between pairs of rat aortic A7r5 myocytes. In intact arterial segments, the peptides desynchronized [Ca2+]i transients in individual SMCs and abolished vasomotion without suppressing Ca2+ transients in individual cells. They also depolarized SMCs, increased [Ca2+]i, and attenuated acetylcholine-induced, endothelium-dependent smooth muscle hyperpolarization. Experiments with endothelium-denuded arteries suggested that the depolarization produced by the peptides under basal conditions was in part secondary to electrical uncoupling of the endothelium from SMCs with loss of a tonic hyperpolarizing effect of the endothelium. Taken together, the results indicate that connexin-mimetic peptides block electrical signaling in rat mesenteric small arteries without exerting major nonjunctional effects.

gap junctions; acetylcholine; endothelium-derived hyperpolarizing factor


Address for reprint requests and other correspondence: V. V. Matchkov, Institute of Physiology and Biophysics, Universitetsparken, Bldg. 160, Univ. of Aarhus, 8000 Aarhus C, Denmark (e-mail: vvm{at}fi.au.dk)




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