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Oxygen glucose deprivation modulates endothelial Ca 2+ signal mediated by TRPV4‐K Ca channels
Author(s) -
Lin Mike T,
Choi ChungSik,
Zha Xiangming,
Yap Fui Chi
Publication year - 2017
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.31.1_supplement.705.2
Subject(s) - transient receptor potential channel , trpv4 , biophysics , chemistry , caveolae , calcium , voltage dependent calcium channel , medicine , endocrinology , receptor , biochemistry , signal transduction , biology , organic chemistry
Endothelial blood brain barrier maintenance and breakdown depend on Ca 2+ magnitude and spatiotemporal dynamics. We have shown that activation of endothelial TRPV4‐K Ca (transient receptor potential vanilloid 4‐calcium‐activated potassium) channels' positive feedback results in microvascular permeability increase and vasogenic edema in a Ca 2+ ‐dependent manner. Mouse cerebral endothelial cells express two types of K Ca channels—SK3 (small K Ca type 3) and IK1 (intermediate K Ca ) channels. Both SK3 and TRPV4 channels reside at caveolae presumably via interaction with caveolar scaffolding protein, caveolin‐1. IK1 channels, however, do not reside at caveolae, suggesting differential TRPV4 Ca 2+ signaling microdomains associated with SK3 and IK1 channels. In this study, we tested whether ischemia/reperfusion modulates TRPV4‐K Ca microdomain Ca 2+ signals. Our results showed that the Ca 2+ signals mediated by TRPV4‐SK3 differed from that mediated by TRPV4‐IK1 channels' positive feedback. SK3‐associated Ca 2+ events showed large amplitude with slow decay kinetic. These events were infrequent compared to that associated with IK1 channels; IK‐associated Ca 2+ events had small amplitude and fast decay kinetics. In response to 60 min of oxygen glucose deprivation (OGD), Ca 2+ events shifted predominately toward that resembling IK1‐associated (frequent Ca 2+ events, small amplitude and fast kinetic). GSK (GSK1016790A, a selective TRPV4 channel agonist; 10 nM) increased Ca 2+ event site and amplitude before OGD; however, after OGD the Ca 2+ signals induced by GSK became Ca 2+ wave‐like events. It is known that low [Ca 2+ ] confined to microdomains maintains junctional protein complexes, whereas large and repetitive Ca 2+ waves induced by ischemia/reperfusion enhance blood brain barrier leakage. Taken together, our results suggest that the Ca 2+ dynamics underlying TRPV4‐K Ca channels' positive feedback may play an important role in blood brain barrier integrity modulation. Support or Funding Information Supported by HL102056 (Lin) and S10 0D020149 (MS Taylor, University of South Alabama).