Boxun Lu, Qi Zhang, Haikun Wang, Yan Wang, Manabu Nakayama, Dejian Ren
Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Neuron 2010 Nov 4In contrast to its extensively studied intracellular roles, the molecular mechanisms by which extracellular Ca(2+) regulates the basal excitability of neurons are unclear. One mechanism is believed to be through Ca(2+)'s interaction with the negative charges on the cell membrane (the charge screening effect). Here we show that, in cultured hippocampal neurons, lowering [Ca(2+)](e) activates a NALCN channel-dependent Na(+)-leak current (I(L-Na)). The coupling between [Ca(2+)](e) and NALCN requires a Ca(2+)-sensing G protein-coupled receptor, an activation of G-proteins, an UNC80 protein that bridges NALCN to a large novel protein UNC79 in the same complex, and the last amino acid of NALCN's intracellular tail. In neurons from nalcn and unc79 knockout mice, I(L-Na) is insensitive to changes in [Ca(2+)](e), and reducing [Ca(2+)](e) fails to elicit the excitatory effects seen in the wild-type. Therefore, extracellular Ca(2+) influences neuronal excitability through the UNC79-UNC80-NALCN complex in a G protein-dependent fashion. Copyright © 2010 Elsevier Inc. All rights reserved.
Boxun Lu, Qi Zhang, Haikun Wang, Yan Wang, Manabu Nakayama, Dejian Ren. Extracellular calcium controls background current and neuronal excitability via an UNC79-UNC80-NALCN cation channel complex. Neuron. 2010 Nov 4;68(3):488-99
PMID: 21040849
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