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Purinergic Signaling Reciprocally Contributes to the TRPV4‐Mediated Mechano‐Sensitive Response in the Aldosterone‐Sensitive Distal Nephron
Author(s) -
Mamenko Mykola,
Zaika Oleg L,
OˈNeil Roger G,
Pochynyuk Oleh
Publication year - 2012
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.26.1_supplement.867.21
Subject(s) - purinergic receptor , extracellular , microbiology and biotechnology , purinergic signalling , receptor , chemistry , stimulation , nephron , medicine , intracellular , endocrinology , biology , kidney , biochemistry , adenosine receptor , agonist
Aldosterone‐sensitive distal nephron (ASDN), which includes the connecting tubule (CNT) and cortical collecting duct (CCD), is essential for regulation of electrolyte balance and circulating volume. Mechanical stimuli affect epithelial transport in ASDN. The ASDN cells respond to mechanical stress by increasing [Ca2+]i. Mechanical stimulation is also known to enhance ATP release from the epithelial cells. P2Y2 receptors play the pivotal role in purinergic signaling in ASDN. Here we combined ratiometric Ca2+ imaging in freshly isolated split‐opened ASDNs with targeted deletion of P2Y2 receptors and TRPV4 channels to test if purinergic signaling contributes to mechano‐sensitive response in the distal nephron. We found that ATP, via stimulation of P2Y2 receptors, increases [Ca2+]i in a biphasic manner: transient Ca2+ peak is followed by a sustained plateau. ATP‐induced [Ca2+]i responses are identical in principal and intercalated cells in CNT and CCD. Both intracellular and extracellular Ca2+ sources account for [Ca2+]i elevation in the ASDN cells. Mechano‐sensitive responses are significantly attenuated in P2Y2 −/− mice. Furthermore, TRPV4 channels are essential for sustained elevation of [Ca2+]i in response to purinergic stimuli. We concluded that reciprocal activation of TRPV4 channels by purinergic cascade is essential for proper mechano‐sensitive response in ASDN.