Premium
Electrical conduction along endothelial cell tubes from mouse feed arteries: confounding actions of glycyrrhetinic acid derivatives
Author(s) -
Behringer Erik J,
Socha Matthew J,
PoloParada Luis,
Segal Steven S
Publication year - 2012
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01814.x
Subject(s) - hyperpolarization (physics) , carbenoxolone , biophysics , gap junction , intracellular , chemistry , membrane potential , biochemistry , biology , stereochemistry , nuclear magnetic resonance spectroscopy
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 (λ) 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 β‐glycyrrhetinic acid (βGA) 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 (λ∼1.4 mm). Propidium iodide injected into one EC spread into surrounding ECs. CBX or βGA inhibited dye transfer, electrical conduction and EC hyperpolarization reversibly. Both agents elevated resting Ca 2+ while βGA 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.