Tuning Electrical Conduction Along Endothelial Tubes of Resistance Arteries Through Ca 2+ -Activated K + Channels

Abstract

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 Ca 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.