title: Tuning electrical conduction along endothelial tubes of resistance arteries through Ca(2+)-activated K(+) channels.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Behringer
authors.forename: Steven S
authors.initials: SS
authors.lastname: Segal
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology; D004553:Electric Conductivity; D004730:Endothelium, Vascular / Q000502:physiology*; D019074:Epigastric Arteries / Q000187:drug effects / Q000502:physiology*; D017629:Gap Junctions / Q000502:physiology*; D007202:Indicators and Reagents / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008839:Microelectrodes; D009569:Nitric Oxide / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D011419:Propidium / Q000493:pharmacokinetics; D012039:Regional Blood Flow / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D052160:Benzothiazoles; D007202:Indicators and Reagents; D024681:Potassium Channels, Calcium-Activated; D014665:Vasodilator Agents; C535212:naphtho(1,2-d)thiazol-2-ylamine; D009569:Nitric Oxide; D011419:Propidium; D000109:Acetylcholine