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1525670 
Journal Article 
Tuning Electrical Conduction Along Endothelial Tubes of Resistance Arteries Through Ca2+-Activated K+ Channels 
Behringer, EJ; Segal, SS 
2012 
Yes 
Circulation Research
ISSN: 0009-7330
EISSN: 1524-4571 
110 
10 
1311-U116 
22492531 
WOS:000303919400011 
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.) 
conducted vasodilation; hyperpolarization; gap junctions; potassium channels; ion channels; membrane potential; conduction; vascular endothelium