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Sympathoexcitation Induced by SK Channel Blockade in PVN Requires Activation of NMDA Receptors
Author(s) -
Larson Robert A,
Chapp Andrew D,
Gu Mingjun,
Chen QingHui
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.932.11
Subject(s) - apamin , chemistry , blockade , nmda receptor , endocrinology , glutamate receptor , medicine , microinjection , rostral ventrolateral medulla , ionotropic effect , channel blocker , receptor , potassium channel , medulla oblongata , pharmacology , central nervous system , calcium
Small conductance calcium activated potassium channels (SK) are abundantly expressed in the paraventricular nucleus (PVN). SK channel blockade in the PVN augments sympathetic nerve activity (SNA), yet the mechanism remains unclear. We hypothesized that the increased SNA evoked by SK channel blockade in PVN requires local activation of glutamate receptors. In anesthetized rats, bilateral PVN microinjection of SK channel blocker Apamin (25 pmol, 50 nl) significantly (n=5; p<0.01) increased splanchnic SNA (SSNA) (304±60%) and mean arterial pressure (MAP) ( 33±6mmHg ). Pre‐treatment with PVN injection of KYN (7.2 nmol), a non‐selective glutamate receptor blocker, significantly attenuated (n=4) the elevated SSNA (137±31%; p<0.05 vs vehicle control) response to Apamin. Similarly, pre‐treatment with AP5 (6.0 nmol), a NMDA receptor blocker, also attenuated (n=4) the SSNA (155±17%; p<0.05 vs vehicle control) response to Apamin. Pre‐treatment with KYN (n=4) and AP5 (n=4) obviously attenuated MAP responses to Apamin (17±6mmHg, p=0.08 for KYN; 14±11mmHg, p=0.06 for AP5) but didn't reach statistical significance. Immunohistochemistry studies demonstrated SK channel expression in PVN neurons with projections to the RVLM. This data indicates that the sympathoexcitatory response elicited by SK channel blockade in PVN, at least partly, requires local activation of NMDA receptors. Support: AHA2640130 (QHC).