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Astrocytes influence SON and PVN neurosecretory and presympathetic neuronal excitability via activation of an extrasynaptic NMDA/A‐type K+ channel coupling mechanism
Author(s) -
Naskar Krishna,
Stern Javier E.
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.1118.35
Subject(s) - chemistry , bursting , excitatory postsynaptic potential , glutamate receptor , astrocyte , medicine , endocrinology , neuroscience , patch clamp , rostral ventrolateral medulla , premovement neuronal activity , blockade , electrophysiology , neuron , biology , central nervous system , medulla oblongata , inhibitory postsynaptic potential , receptor
We showed that activation of extrasynaptic NMDARs (eNMDARs) by ambient glutamate under astrocytic control inhibited the voltage‐gated K+ current I A in neurosecretory vasopressin (VP) and PVN‐RVLM presympathetic neurons. Here, we aimed to address: i) whether the eNMDARs/I A coupling increases the firing activity of neurosecretory and presympathetic PVN neurons, and ii) whether this effect involves an imbalanced interaction with the opposing I T Ca 2+ current. Patch clamp recordings were obtained from identified eGFP‐VP and PVN‐RVLM neurons. We found that activation of eNMDARs following blockade of astrocyte glutamate transporters (DHK 300μM) increased the firing activity of VP and PVN‐RVLM neurons in response to depolarizing pulses (~62%, P <0.05). This effect involved shorter latency to first spike, increased total number of action potentials, and duration of firing burst. These effects were prevented following I A blockade with 4AP (P>;0.2 in 4AP). In the presence of the I T channel blockade (mibefradil), the DHK excitatory effect was reduced to ~30%, P<0.05). Our studies indicate that activation of eNMDARs increases neuronal excitability of hypothalamic neurons by inhibiting I A function, an effect that is in part dependent on an enhanced activation of I T . Thus, the eNMDAR/I A coupling stands as a functionally relevant mechanism by which astrocytes influence hypothalamic neurohumoral outflow.