Tuning Electrical Conduction Along Endothelial Tubes of Resistance Arteries Through Ca2+-Activated K+ Channels
Rationale: Electric 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 electric 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 electric 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 electric 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 electric 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 electric conduction (ie, changes in Vm) by ≈30% (P<0.05).
Conclusions: These findings illustrate a novel role for SKCa/IKCa activity in tuning electric conduction along the endothelium of resistance vessels by governing signal dissipation through changes in membrane resistance. Voltage-insensitive ion channels can thereby tune intercellular electric signaling independent from gap junction channels.
- conducted vasodilation
- gap junctions
- potassium channels
- ion channels
- membrane potential
- vascular endothelium
- Received December 9, 2011.
- Revision received March 26, 2012.
- Accepted March 29, 2012.
- © 2012 American Heart Association, Inc.