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Role of small conductance calcium‐activated potassium channels (SK2) expressed in hypothalamic PVN neurons in regulating sympathetic nerve activity (SNA) in rats
Author(s) -
Gui Le,
Gu Mingjun,
LaGrange Lila P,
Zhu Jianghua,
Chen Qing-Hui
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.1091.50
Subject(s) - apamin , sk channel , rostral ventrolateral medulla , medicine , endocrinology , microinjection , chemistry , calcium activated potassium channel , potassium channel , medulla oblongata , neuroscience , ion channel , biology , central nervous system , receptor
Recently, we reported that SK channels regulate membrane properties of RVLM projecting PVN neurons and that inhibition of SK channels increase in vitro excitability. Here, we determined in vivo the role of PVN SK channels in regulating SNA and mean arterial pressure (MAP). In anesthetized rats, bilateral PVN microinjection of SK channel blockade with apamin (0, 0.125, 1.25, 3.75, 12.5, 25 pmol; 50 nl) increased splanchnic SNA (SSNA), renal SNA (RSNA), and MAP in a dose‐dependent manner. Maximum increases in SNA and MAP elicited by apamin (12.5 pmol) in SSNA, RSNA and MAP were 330 ± 40% (n=8), 271 ± 40% (n=6), and 29 ± 4 mmHg (n=7), respectively. Pre‐treatment with DCEBIO (2.5 nmol), a SK channel opener, microinjected into the PVN significantly (p<0.05–0.001, n=5) diminished the sympathoexcitatory response evoked by apamin (102 ± 24% for SSNA, 78 ± 40% for RSNA and 16 ± 3 mmHg for MAP). DCEBIO alone was without effect on baseline SNA and MAP. Western‐blot examination of the PVN showed abundant protein expression of SK2 channels. Further immunohistochemistry studies showed that SK2 channels were primarily expressed in dorsal and lateral parvocellular divisions of the PVN. The majority of SK2 channel expression was localized in PVN‐RVLM neurons identified by retrograde labeling. We conclude that SK currents in the PVN inhibit ongoing SNA. Inhibition of SK2 channels may underlie the mechanism of increased SNA induced by apamin. Support: AHA 10SDG2640130 (QHC).