Muscarinic receptor activation modulates the excitability of hilar mossy cells through the induction of an afterdepolarization.

Muscarinic receptor activation modulates the excitability of hilar mossy cells through the induction of an afterdepolarization.
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DOI:
10.1016/j.brainres.2010.01.011
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发表时间:
2010-03-08
期刊:
影响因子:
2.9
通讯作者:
Frazier, Charles J.
Frazier, Charles J.
中科院分区:
医学3区
文献类型:
--
作者:
Hofmann, Mackenzie E.;Frazier, Charles J.

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In the present study we used electrophysiological techniques in an in vitro preparation of the rat dentate gyrus to examine the effect of muscarinic acetylcholine receptor activation on the intrinsic excitability of hilar neurons. We found that bath application of muscarine caused a direct depolarization in approximately eighty percent of mossy cells tested, and also produced a clear afterdepolarization (ADP) in nearly one hundred percent of trials. The ADP observed in hilar mossy cells is produced by opening of a Na+ permeant and yet largely TTX insensitive ion channel. It requires an increase in postsynaptic calcium for activation, and is blocked by flufenamic acid, an antagonist of a previously identified calcium activated non-selective cation channel (ICAN). Further, we demonstrate that induction of an ADP in current clamp causes release of cannabinoids, and subsequent depression of GABAergic transmission that is comparable to that produced in the same cells by a more conventional five second depolarization in voltage clamp. By contrast, other types of hilar neurons were less strongly depolarized by bath application of muscarinic agonists, and uniformly lacked a similar muscarinic ADP. Overall, the data presented here extend our understanding of the specific mechanisms through which muscarinic agonists are likely to modulate neuronal excitability in the hilar network, and further reveal a mechanism that could plausibly promote endocannabinoid mediated signaling in vivo.
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