Premium
Acute Ischemia Activates Distinct Ion Currents in Endothelial Cells and Pericytes of Capillaries in Guinea Pig Cochlear Lateral Wall
Author(s) -
Yang Yuqin,
Nuttall Alfred L,
Jiang ZhiGen
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.687.4
Subject(s) - niflumic acid , biophysics , chemistry , spiral ganglion , spiral ligament , patch clamp , guinea pig , reversal potential , cochlea , endothelial stem cell , anatomy , medicine , biochemistry , biology , organ of corti , in vitro , receptor
Capillary blood flow in spiral ligament (SL) and strial vascularis (SV) of the cochlear lateral wall are critical for cochlear health and to meet the high energy‐demand of auditory transduction, but the physio‐pathology of the local capillary cells remains poorly understood. Using acutely isolated capillary segments and whole‐cell recording techniques, we characterized the main membrane currents and the responses to acute ischemic treatment (AIT, hypercapnic pH 6.2, pO 2 =0 mmHg) of the endothelial cells (EC) and pericytes (PC) in the SL and SV. We found: 1) In physiological solutions, the PCs, but not ECs, showed a [K + ] o ‐regulated and Ba 2+ ‐sensitive inward rectifier current (Kir). 2) ECs, but PCs rarely, showed a significant outward rectifier current, which was inhibited by 1 mM 4‐AP, 100 μM niflumic acid (NFA) but not TEA. 3) When recorded in situ of a vessel segment, both types of cells showed variable electrical coupling that was blocked by 30 μM 18β‐glycyrrhetinic acid or 100 μM 2‐APB. 4) AIT (3 – 24 min) caused a reversible and partially repeatable outward current at holding potential −20 mV in isolated ECs and PCs. The AIT‐activated net current had I‐V curves and kinetics which mostly resemble to those of Ca 2+− activated Cl − channels: strong outward rectification with quick or slow time course to reach steady‐state within 0.5 – 2 s voltage steps. This AIT‐induced current was inhibited by niflumic acid and 1 mM TEA but not 4‐AP. 5) AIT (>;3 min) also inhibited gap junction coupling current. We conclude that the capillary EC and PC in the SV and SL express different K + ‐channels, suggesting a role of PCs as the K + ‐sensor for blood flow regulation, and the acute ischemia activates chloride channels and BK channels likely via elevation of cytosolic Ca 2+ in both ECs and PCs. Supported by NIH grants DC004716 (ZGJ) and DC005983, DC 00105 (ALN).