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

Rationale: Electrical conduction through gap junction channels between endothelial cells of resistance vessels is integral to blood flow control. Small and intermediate-conductance Ca2+-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 mu m wide; 1-3 mm long; cell length, approximate to 35 mu m) 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 (V-m) at site 2 (separation distance =50-2000 mu m). SKCa/IKCa activation (NS309, 1 mu mol/L) reduced the change in V-m along endothelial cell tubes by >= 50% and shortened the electrical length constant (lambda) from 1380 to 850 mu m (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 approximate to 10 mV and enhanced electrical conduction (ie, changes in V-m) by approximate to 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. (Circ Res. 2012;110:1311-1321.)