Neuronal Nitric Oxide Synthase Regulates Cerebellar Parallel Fiber Slow EPSC in Purkinje Neurons by Modulating STIM1-Gated TRPC3-Containing Channels.

Autor: Gui L; Robarts Research Institute, University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Tellios V; Graduate Program of Neuroscience, University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Xiang YY; Robarts Research Institute, University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada., Feng Q; Department of Physiology and Pharmacology, University of Western, Ontario1151 Richmond Street North, London, ON, N6A 5B7, Canada., Inoue W; Robarts Research Institute, University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada. winoue@uwo.ca.; Graduate Program of Neuroscience, University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada. winoue@uwo.ca.; Department of Physiology and Pharmacology, University of Western, Ontario1151 Richmond Street North, London, ON, N6A 5B7, Canada. winoue@uwo.ca., Lu WY; Robarts Research Institute, University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada. wlu53@uwo.ca.; Graduate Program of Neuroscience, University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada. wlu53@uwo.ca.; Department of Physiology and Pharmacology, University of Western, Ontario1151 Richmond Street North, London, ON, N6A 5B7, Canada. wlu53@uwo.ca.
Jazyk: angličtina
Zdroj: Cerebellum (London, England) [Cerebellum] 2024 Oct; Vol. 23 (5), pp. 1867-1881. Date of Electronic Publication: 2024 Mar 12.
DOI: 10.1007/s12311-024-01683-0
Abstrakt: Responding to burst stimulation of parallel fibers (PFs), cerebellar Purkinje neurons (PNs) generate a convolved synaptic response displaying a fast excitatory postsynaptic current (EPSC Fast ) followed by a slow EPSC (EPSC Slow ). The latter is companied with a rise of intracellular Ca 2+ and critical for motor coordination. The genesis of EPSC Slow in PNs results from activation of metabotropic type 1 glutamate receptor (mGluR1), oligomerization of stromal interaction molecule 1 (STIM1) on the membrane of endoplasmic reticulum (ER) and opening of transient receptor potential canonical 3 (TRPC3) channels on the plasma membrane. Neuronal nitric oxide synthase (nNOS) is abundantly expressed in PFs and granule neurons (GNs), catalyzing the production of nitric oxide (NO) hence regulating PF-PN synaptic function. We recently found that nNOS/NO regulates the morphological development of PNs through mGluR1-regulated Ca 2+ -dependent mechanism. This study investigated the role of nNOS/NO in regulating EPSC Slow . Electrophysiological analyses showed that EPSC Slow in cerebellar slices of nNOS knockout (nNOS -/- ) mice was significantly larger than that in wildtype (WT) mice. Activation of mGluR1 in cultured PNs from nNOS -/- mice evoked larger TRPC3-channel mediated currents and intracellular Ca 2+ rise than that in PNs from WT mice. In addition, nNOS inhibitor and NO-donor increased and decreased, respectively, the TRPC3-current and Ca 2+ rise in PNs. Moreover, the NO-donor effectively decreased TRPC3 currents in HEK293 cells expressing WT STIM1, but not cells expressing a STIM1 with cysteine mutants. These novel findings indicate that nNOS/NO inhibits TRPC3-containig channel mediated cation influx during EPSC Slow , at least in part, by S-nitrosylation of STIM1.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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