Tuning Electrical Conduction Along Endothelial Tubes of Resistance Arteries Through Ca2+-Activated K+ Channels

• Published in: Circulation research Vol. 110; no. 10; pp. 1311 - 1321
• Main Authors: Behringer, Erik J, Segal, Steven S
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 11.05.2012; Lippincott Williams & Wilkins
• Subjects: Acetylcholine; Arteries; Biological and medical sciences; Conduction; Endothelial cells; Endothelium; Fundamental and applied biological sciences. Psychology; Gap junctions; Hyperpolarization; Ion channels; Membrane potential; Membrane resistance; Microelectrodes; Potassium channels (calcium-gated); propidium iodide; Skeletal muscle; Skin; Vertebrates: cardiovascular system; gap junctions; Calcium; Electrophysiology; Cell junction; Electrical conduction; Ionic channel; Inorganic element; Artery; Gap junction; Vasodilation; conducted vasodilation; ion channels; Endothelium; Vasomotricity; Vertebrata; vascular endothelium; Mammalia; Blood vessel; potassium channels; conduction; Circulatory system; Membrane potential; Potassium; Hyperpolarization
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/CIRCRESAHA.111.262592

RATIONALE:Electrical conduction through gap junction channels between endothelial cells of resistance vessels is integral to blood flow control. Small and intermediate-conductance Ca-activated K channels (SKCa/IKCa) initiate electrical signals in endothelial cells, but it is unknown whether SKCa/IKCa activation alters signal transmission along the endothelium. OBJECTIVE:We tested the hypothesis that SKCa/IKCa activity regulates electrical conduction along the endothelium of resistance vessels. METHODS AND RESULTS:Freshly isolated endothelial cell tubes (60 μm wide; 1–3 mm long; cell length, ≈35 μm) from mouse skeletal muscle feed (superior epigastric) arteries were studied using dual intracellular microelectrodes. Current was injected (±0.1–3 nA) at site 1 while recording membrane potential (Vm) at site 2 (separation distance=50–2000 μm). SKCa/IKCa activation (NS309, 1 μmol/L) reduced the change in Vm along endothelial cell tubes by ≥50% and shortened the electrical length constant (λ) from 1380 to 850 μm (P<0.05) while intercellular dye transfer (propidium iodide) was maintained. Activating SKCa/IKCa with acetylcholine or SKA-31 also reduced electrical conduction. These effects of SKCa/IKCa activation persisted when hyperpolarization (>30 mV) was prevented with 60 mmol/L [K]o. Conversely, blocking SKCa/IKCa (apamin+charybdotoxin) depolarized cells by ≈10 mV and enhanced electrical conduction (ie, changes in Vm) by ≈30% (P<0.05). CONCLUSIONS:These findings illustrate a novel role for SKCa/IKCa activity in tuning electrical conduction along the endothelium of resistance vessels by governing signal dissipation through changes in membrane resistance. Voltage-insensitive ion channels can thereby tune intercellular electrical signaling independent from gap junction channels.