Tuning electrical conduction along endothelial tubes of resistance arteries through Ca ²⁺-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 Ca ²⁺-activated K channels (SK _Ca/IK _Ca) initiate electrical signals in endothelial cells, but it is unknown whether SK _Ca/IK _Ca activation alters signal transmission along the endothelium. Objective: We tested the hypothesis that SK _Ca/IK _Ca 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 (V _m) at site 2 (separation distance=50-2000 μm). SK _Ca/IK _Ca activation (NS309, 1 μmol/L) reduced the change in V _m 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 SK _Ca/IK _Ca with acetylcholine or SKA-31 also reduced electrical conduction. These effects of SK _Ca/IK _Ca activation persisted when hyperpolarization (>30 mV) was prevented with 60 mmol/L [K ⁺] _o. Conversely, blocking SK _Ca/IK _Ca (apamin+charybdotoxin) depolarized cells by ≈10 mV and enhanced electrical conduction (ie, changes in V _m) by ≈30% (P<0.05). Conclusions: These findings illustrate a novel role for SK _Ca/IK _Caactivity 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.