Loss of β2-laminin alters calcium sensitivity and voltage gated calcium channel maturation of neurotransmission at the neuromuscular junction

Chand, Kirat K., Lee, Kah Meng, Schenning, Mitja P., Lavidis, Nickolas A. and Noakes, Peter G. (2015) Loss of β2-laminin alters calcium sensitivity and voltage gated calcium channel maturation of neurotransmission at the neuromuscular junction. Journal of Physiology, 593 1: 245-265. doi:10.1113/jphysiol.2014.284133

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Author Chand, Kirat K.
Lee, Kah Meng
Schenning, Mitja P.
Lavidis, Nickolas A.
Noakes, Peter G.
Title Loss of β2-laminin alters calcium sensitivity and voltage gated calcium channel maturation of neurotransmission at the neuromuscular junction
Journal name Journal of Physiology   Check publisher's open access policy
ISSN 1469-7793
0022-3751
Publication date 2015-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.1113/jphysiol.2014.284133
Volume 593
Issue 1
Start page 245
End page 265
Total pages 21
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell
Collection year 2015
Language eng
Abstract β2-laminin is a key mediator in the differentiation and formation of the skeletal neuromuscular junction. Loss of β2-laminin results in significant structural and functional aberrations such as decreased number of active zones and reduced spontaneous release of transmitter. In vitro β2-laminin has been shown to bind directly to the pore forming subunit of P/Q-type voltage-gated calcium channels (VGCCs). Neurotransmission is initially mediated by N-type VGCCs, but by postnatal day 18 switches to P/Q-type VGCC dominance. The present study investigated the changes in neurotransmission during the switch from N- to P/Q-type VGCC-mediated transmitter release at β2-laminin-deficient junctions. Analysis of the relationship between quantal content and extracellular calcium concentrations demonstrated a decrease in the calcium sensitivity, but no change in calcium dependence at β2-laminin-deficient junctions. Electrophysiological studies on VGCC sub-types involved in transmitter release indicate N-type VGCCs remain the primary mediator of transmitter release at matured β2-laminin-deficient junctions. Immunohistochemical analyses displayed irregularly shaped and immature β2-laminin-deficient neuromuscular junctions when compared to matured wild-type junctions. β2-laminin-deficient junctions also maintained the presence of N-type VGCC clustering within the presynaptic membrane, which supported the functional findings of the present study. We conclude that β2-laminin is a key regulator in development of the NMJ, with its loss resulting in reduced transmitter release due to decreased calcium sensitivity stemming from a failure to switch from N- to P/Q-type VGCC-mediated synaptic transmission.
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Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
School of Biomedical Sciences Publications
 
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Created: Thu, 11 Dec 2014, 08:47:30 EST by Debra McMurtrie on behalf of Queensland Brain Institute