Intercellular electrical communication among smooth muscle and endothelial cells in guinea‐pig mesenteric arterioles

Abstract

1. Current clamp studies using two patch electrodes and morphological observations have been performed in guinea-pig mesenteric arterioles to evaluate intercellular electrical couplings.2. In electron micrographs, preparations were found to have a single layer of smooth muscle cells. Typical gap junctions were readily observed between endothelial cells only.3. While immunoreactivity to connexin 40 was strongly expressed on the membranes of endothelial cells only, that to connexin 43 was expressed on both smooth muscle and endothelial cell membranes.4. Neurobiotin injected into a smooth muscle cell diffused into several neighbouring smooth muscle cells while that injected into an endothelial cell diffused into many endothelial cells.5. Acetylcholine-induced hyperpolarizations were conducted from endothelial cells to smooth muscle cells with a relative amplitude of 80.1 %. Ba 2+-induced action potentials were conducted in the opposite direction with a relative amplitude of 92.4 %.6. An electrotonic potential produced in a smooth muscle cell by current injection diminished steeply with distance as it spread along the muscle layer, plateauing at distances beyond 25 µm. An electrotonic potential produced in an endothelial cell spread within the intima with virtually no reduction. Electrotonic potentials could conduct through myoendothelial couplings, which seemed to behave as ohmic resistors without rectification.7. The coupling resistance between adjacent smooth muscle cells was estimated to be at least 90 MΩ and that between a smooth muscle cell and the whole endothelial layer to be 0.9 GΩ.8. The results indicate that although the resistance of myoendothelial couplings is appreciable, the endothelium may be important as a low resistance path connecting many smooth muscle cells.

Thromboxane receptor stimulation associated with loss of SKCa activity and reduced EDHF responses in the rat isolated mesenteric artery

“…The hyperpolarization reflects the action of a factor (EDHF) and/or the spread of current from the endothelium through heterocellular (myoendothelial) gap junctions. Physiologically, EDHF appears to provide an important route to vasodilatation, which assumes increasing importance over NO with decreasing arterial size, predominating in resistance arteries and arterioles and operating in vivo (Yamamoto et al, 2001;Busse et al, 2002;Parkington et al, 2002). Therefore, the possibility that an autacoid like TXA 2 could influence the ability of the endothelium locally to modulate the arterial diameter through EDHF is clearly of applied interest.…”

cAMP facilitates EDHF-type relaxations in conduit arteries by enhancing electrotonic conduction via gap junctions

“…Such direct intercellular communication depends on the coupling of apposing cells by gap junctions, which are constructed from connexin (Cx) proteins and possess an aqueous central pore (5). In arterioles, myoendothelial gap junctions behave as simple ohmic resistors without rectification, so that complex electrical events are reduced in amplitude by 10-20% when conducted between the endothelium and media in either direction, but are preserved in temporal form (4). By contrast, in thick-walled arteries, it has been argued that the endothelium cannot act as a significant source of hyperpolarizing current because the large bulk of the media will result in current dissipation (6).…”

“…In guinea pig and hamster arterioles, hyperpolarizations induced either by ACh or the injection of electrical current into the endothelium may be transmitted to smooth muscle cells through a passive electrotonic mechanism, and in the converse sense, action potentials originating in smooth muscle cells can be detected in the endothelium (2)(3)(4). Such direct intercellular communication depends on the coupling of apposing cells by gap junctions, which are constructed from connexin (Cx) proteins and possess an aqueous central pore (5).…”

Analysis of acetylcholine-induced membrane responses in vascular endothelial cells of the guinea-pig mesenteric artery using mefloquine as a gap junction blocker

“…In vascular endothelial cells, vasoactive substances such as acetylcholine (ACh) induce membrane hyperpolarization, which then conducts to surrounding smooth muscle cells via Correspondence to: Yoshimichi Yamamoto, M.D., Ph.D., Department of Cell Physiology, Nagoya City University Graduate School of Medical Sciences, Mizuho-Ku, Nagoya 467-8601, Japan Phone: +81-52-853-8131, 8863 Fax: +81-52-842-1538 e-mail: yyamamot@med.nagoya-cu.ac.jp myoendothelial gap junctions to produce vasodilation (Yamamoto et al, 1999;Yamamoto et al, 2001). ACh and other agonists increase the intracellular concentration of Ca 2+ ([Ca 2+ ]i), which in turn activates both IKCa (KCa3.1) and SKCa (KCa2.3) channels in many types of vessels.…”