PMID- 22168386
OWN - NLM
STAT- MEDLINE
DCOM- 20120907
LR  - 20211021
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 166
IP  - 2
DP  - 2012 May
TI  - Electrical conduction along endothelial cell tubes from mouse feed arteries: 
      confounding actions of glycyrrhetinic acid derivatives.
PG  - 774-87
LID - 10.1111/j.1476-5381.2011.01814.x [doi]
AB  - BACKGROUND AND PURPOSE: Electrical conduction along endothelium of resistance 
      vessels has not been determined independently of the influence of smooth muscle, 
      surrounding tissue or blood. Two interrelated hypotheses were tested: (i) 
      Intercellular conduction of electrical signals is manifest in endothelial cell 
      (EC) tubes; and (ii) Inhibitors of gap junction channels (GJCs) have confounding 
      actions on EC electrical and Ca(2+) signalling. EXPERIMENTAL APPROACH: Intact EC 
      tubes were isolated from abdominal muscle feed (superior epigastric) arteries of 
      C57BL/6 mice. Hyperpolarization was initiated with indirect (ACh) and direct 
      (NS309) stimulation of intermediate- and small-conductance Ca(2+) -activated K(+) 
      channels (IK(Ca) /SK(Ca) ). Remote membrane potential (V(m) ) responses to 
      intracellular current injection defined the length constant (lambda) for electrical 
      conduction. Dye coupling was evaluated following intracellular microinjection of 
      propidium iodide. Intracellular Ca(2+) dynamics were determined using Fura-2 
      photometry. Carbenoxolone (CBX) or beta-glycyrrhetinic acid (betaGA) was used to 
      investigate the role of GJCs. KEY RESULTS: Steady-state V(m) of ECs was -25 mV. 
      ACh and NS309 hyperpolarized ECs by -40 and -60 mV respectively. Electrical 
      conduction decayed monoexponentially with distance (lambda approximately 1.4 mm). Propidium iodide 
      injected into one EC spread into surrounding ECs. CBX or betaGA inhibited dye 
      transfer, electrical conduction and EC hyperpolarization reversibly. Both agents 
      elevated resting Ca(2+) while betaGA inhibited responses to ACh. CONCLUSIONS AND 
      IMPLICATIONS: Individual cells were effectively coupled to each other within EC 
      tubes. Inhibiting GJCs with glycyrrhetinic acid derivatives blocked 
      hyperpolarization mediated by IK(Ca) /SK(Ca) channels, regardless of Ca(2+) 
      signalling, obviating use of these agents in distinguishing key determinants of 
      electrical conduction along the endothelium.
CI  - (c) 2011 The Authors. British Journal of Pharmacology (c) 2011 The British 
      Pharmacological Society.
FAU - Behringer, Erik J
AU  - Behringer EJ
AD  - Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, 
      USA.
FAU - Socha, Matthew J
AU  - Socha MJ
FAU - Polo-Parada, Luis
AU  - Polo-Parada L
FAU - Segal, Steven S
AU  - Segal SS
LA  - eng
GR  - R01 HL086483/HL/NHLBI NIH HHS/United States
GR  - F32-HL110701/HL/NHLBI NIH HHS/United States
GR  - R37-HL041026/HL/NHLBI NIH HHS/United States
GR  - F32 HL107050/HL/NHLBI NIH HHS/United States
GR  - F32-HL107050/HL/NHLBI NIH HHS/United States
GR  - R37 HL041026/HL/NHLBI NIH HHS/United States
GR  - F32 HL110701/HL/NHLBI NIH HHS/United States
GR  - R01-HL086483/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (6,7-dichloro-1H-indole-2,3-dione 3-oxime)
RN  - 0 (Indoles)
RN  - 0 (Intermediate-Conductance Calcium-Activated Potassium Channels)
RN  - 0 (Kcnn3 protein, mouse)
RN  - 0 (Kcnn4 protein, mouse)
RN  - 0 (Oximes)
RN  - 0 (Small-Conductance Calcium-Activated Potassium Channels)
RN  - MM6384NG73 (Carbenoxolone)
RN  - N9YNS0M02X (Acetylcholine)
RN  - P540XA09DR (Glycyrrhetinic Acid)
SB  - IM
MH  - Abdomen
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Arteries/drug effects/*physiology
MH  - Carbenoxolone/pharmacology
MH  - *Electric Conductivity
MH  - Endothelial Cells/drug effects/*physiology
MH  - Gap Junctions/drug effects/*physiology
MH  - Glycyrrhetinic Acid/pharmacology
MH  - Indoles/pharmacology
MH  - Intermediate-Conductance Calcium-Activated Potassium Channels/physiology
MH  - Membrane Potentials
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Muscle, Skeletal/physiology
MH  - Oximes/pharmacology
MH  - Small-Conductance Calcium-Activated Potassium Channels/physiology
PMC - PMC3417504
EDAT- 2011/12/16 06:00
MHDA- 2012/09/08 06:00
PMCR- 2013/05/01
CRDT- 2011/12/16 06:00
PHST- 2011/12/16 06:00 [entrez]
PHST- 2011/12/16 06:00 [pubmed]
PHST- 2012/09/08 06:00 [medline]
PHST- 2013/05/01 00:00 [pmc-release]
AID - 10.1111/j.1476-5381.2011.01814.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 2012 May;166(2):774-87. doi: 10.1111/j.1476-5381.2011.01814.x.