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Ischemic treatment hyperpolarizes cochlear arteriolar smooth muscle and endothelial cells via different channel mechanisms
Author(s) -
Jiang ZhiGen,
Yang Yuqin
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.687.5
Subject(s) - niflumic acid , depolarization , vasodilation , hyperpolarization (physics) , chemistry , reversal potential , biophysics , membrane potential , medicine , electrophysiology , pacemaker potential , conductance , ischemia , patch clamp , biology , stereochemistry , mathematics , combinatorics , nuclear magnetic resonance spectroscopy
Regional acute ischemia generally induces a compensatory vasodilation in the most vascular beds including the cochlear arterioles but the underlying cellular mechanism remains controversial. Using conventional intracellular and whole‐cell recording from smooth muscle (SMC) and endothelial cells (EC) in situ of and dispersed from segments of guinea pigs cochlear spiral modiolar artery, we analyzed the membrane actions of acute ischemic treatment (AIT, hypercapinic hypoxia, pO 2 =0 mmHg, pH=6.2). The AIT for 2 to 20 min caused a reversible and partially repeatable vasodilation and a hyperpolarization in the majority of cells. ACh‐ and 10 mM K + ‐induced dilation was significantly reduced, lost or reversed to a constriction during and after the AIT. Holding at −20 mV, AIT induced a reversible 10–65 pA outward current within 1–2 min in the majority of SMCs and ECs. During the AIT, the whole‐cell I/V curve became stronger outwardly rectifying at voltages >; −40 mV. The AIT‐induced net current in isolated SMCs exhibited a delayed outward rectification upon depolarization steps and partial blockade by 1–10 mM TEA or 4‐AP, suggesting an activation of both voltage‐gated (K V ) and big conductance Ca 2+ ‐activated (BK) K + ‐channels. In contrast, the AIT‐induced current in isolated ECs was blocked by 30 μM niflumic acid but not by TEA, 4‐AP and linopirdine; the net current showed a voltage and time dependence typical of Ca 2+ ‐activated Cl − ‐channels (CaCC): slowly activating outwardly rectifying with a reversal potential near −30 mV. AIT (>;10 min) also reduced gap junction coupling current in in situ SMCs and ECs. We conclude that the acute ischemia in the cochlear arteriole induces hyperpolarization, dilation and loss of EDHF function via activation of K V and BK in smooth muscle cells and activation of Ca 2+ ‐activated Cl − ‐channels in endothelial cells, as well as an inhibition of gap junction coupling. Supported by NIH NIDCD DC 004716, P30 05983.