Role of Heterocellular Gap Junctional Communication in Endothelium-Dependent Smooth Muscle Hyperpolarization: Inhibition by a Connexin-Mimetic Peptide

Abstract

A synthetic connexin-mimetic peptide (Gap 27 peptide) was used to evaluate the contribution of gap junctional communication to smooth muscle responses mediated by the endothelium-dependent agonist acetylcholine (ACh) in rabbit mesenteric arteries. Hyperpolarizations and relaxations to 0.1 and 1 μM ACh observed in the presence of nitric oxide synthase and cyclooxygenase inhibition were markedly attenuated by the peptide at a concentration of 300 μM, whereas the hyperpolarizing response to levcromakalim, aKATPchannel opener, was unaffected. The peptide also attenuated intercellular transfer of Lucifer yellow in confluent cultures of COS-7 cells, thus confirming its ability to modulate the permeability of gap junctions. The findings demonstrate that heterocellular gap junctional communication contributes to NO- and prostanoid-independent mechanisms of vasorelaxation that are widely attributed to an endothelium-derived hyperpolarizing factor.