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; Lavidis, Nickolas A.; Noakes, Peter G.

doi:10.1113/jphysiol.2014.284133

Cited by 33 publications

(58 citation statements)

References 70 publications

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“…However, the synergism between a defect of LAMA1 and that of a Ca 2ϩ -related protein is not as immediately obvious as that of the PMCA2 pump with Ca 2ϩ -related Cadherin-23 in hereditary deafness. It might be interesting that another laminin, ␤-2 laminin, has recently been shown to be involved in the process of maturation and Ca 2ϩ sensitivity of voltage-gated Ca 2ϩ channels (31).…”

Section: Discussionmentioning

confidence: 99%

A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1α Mutations

Calì¹,

Lopreiato

Shimony

et al. 2015

Journal of Biological Chemistry

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Background: Mutations in plasma membrane Ca 2ϩ -ATPase (PMCA) isoform 3 and in laminin subunit 1␣ have previously been linked to ataxic phenotypes. Results: A novel PMCA3 missense mutation co-occurring with a compound heterozygous mutation in laminin subunit 1␣ impaired cellular Ca 2ϩ homeostasis. Conclusion:The two mutations could work synergistically to generate the disease phenotype. Significance: A digenic mechanism could be responsible for this case of cerebellar ataxia.

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Section: Discussionmentioning

confidence: 99%

A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1α Mutations

Calì¹,

Lopreiato

Shimony

et al. 2015

Journal of Biological Chemistry

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“…Electrophysiological and contractile experimentation were conducted as described previously. 7,16 For electrophysiological experimentation,…”

Section: Animalsmentioning

confidence: 99%

“…Electrophysiological and contractile experimentation were conducted as described previously. 7,16 For electrophysiological experimentation,-5 M to 4.31×10 -3 M) and 1-heptanol (7.07×10 -5 M to 3.54×10 -3 M) were examined. For contractile experimentation, noradrenaline (1×10 -9 M to 3×10 -4 M) was utilised to evoke contractions in the absence and presence of 1,…”

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confidence: 99%

Modulation of Smooth Muscle Relaxation by Short and Long Carbon Based Chemicals

Poyton¹,

Cheesman²,

Manchadi³

et al. 2015

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Introduction: Short and long-chained based carbon chemicals derived from plants are found in many household products and are widely used in complementary medicine. It has been suggested anecdotally that some of these chemicals have the ability to relax smooth muscle tissues, and to test this concept, this study examines the effects of 1,8-cineole, 1-heptanol, α-pinene, cis-3-hexen-1-ol and trans-2-hexenal on neurotransmission and contraction of mouse and rat vas deferens. Methods: Focal extracellular recordings from the surface of mouse vas deferens of electricallyevoked nerve terminal impulses (NTIs) and electrically-evoked excitatory junctional currents (EJCs) were examined in both the presence and the absence of each chemical. Likewise, noradrenaline-evoked contractile forces of rat vas deferens were examined in both the presence and the absence of each chemical. Results: Relative to the respective controls, 1,8-cineole, 1-heptanol and trans-2-hexenal each statistically significantly decreased both smooth muscle contractile forces and EJC amplitudes, with 1-heptanol and trans-2-hexenal also statistically significantly decreasing NTI amplitudes. On NTI and EJC amplitudes the effects of 1,8-cineole and 1-heptanol were reversible whereas the effects of trans-2-hexenal were irreversible. Conclusion: Our results demonstrate that 1,8-cineole and trans-2-hexenal decrease smooth muscle neurotransmission and contraction and thereby cause smooth muscle relaxation, thus suggesting that these chemicals may have clinical applications and health benefits.Key words: 1,8-cineole, cis-3-hexen-1-ol, 1-heptanol, α-pinene, smooth muscle, relaxation, trans-2-hexenal. SUMMARY• 1,8-Cineole, 1-heptanol and trans-2-hexenal decrease nerve terminal impulse (NTI) amplitudes and smooth muscle contractile forces.• 1,8-Cineole, 1-heptanol and trans-2-hexenal also decrease excitatory junction current (EJC) amplitudes.• Reductions in NTIs and EJCs by 1-heptanol and 1,8-cineole were reversible, but reductions caused by trans-2-hexenal were irreversible.• Minor structural differences between the chemicals can lead to significant changes in their effects on smooth muscle neurotransmission and contraction. PICTORIAL ABSTRACTAbbreviations used: ATP: Adenosine 5'-triphosphate, EJC: Excitatory junction current, NTI: Nerve terminal impulse. Correspondence:Matthew James Cheesman, School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, 4072, Australia.Email: m.cheesman@uq.edu.au DOI : 10.5530/pc.2015.4.6 INTRODUCTIONPlant-derived chemicals are found in many household products and are widely used in complementary medicines for their fragrance and perceived soothing or calming effects. 1-3 Beyond these sensory and psychological benefits, the topical use of some plant-derived chemicals has been shown to cause smooth muscle relaxation. [4][5][6][7] The long-chained plantderived carbon based chemicals 1,8-cineole ( Figure 1a) and α-pinene ( Figure 1b) and the short-chained plant-derived carbon based chemicals cis-3-hexen-...

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“…Disruption of these components may result in altered efficiency of neurotransmission at the synapse (Li et al, 1995;Knight et al, 2003;Urbano et al, 2003;Depetris et al, 2008;Chand et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…These laminin heterotrimers comprise of individual laminin chains; α2, α4, α5, β2 and γ1 . Laminin-β2 chain is involved in the development and maturation of the NMJ via its interaction and subsequent involvement in the developmental switch of the voltage-gated calcium channels (Nishimune et al, 2004;Chand et al, 2015). Laminin-α4 is suggested to be important for the maintenance of the NMJ, with the loss of this laminin resulting in premature ageing (Samuel et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

The role of synaptic laminins-α4 and -β2 in maturation and maintenance of the neuromuscular synapse

Lee¹

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The proper development, maturation and maintenance of the neuromuscular junction (NMJ) are critical for ensuring efficient neurotransmission. Proteins found within the basal lamina of the synaptic cleft, namely the laminins family, are heavily involved in maintaining normal structure and function of the NMJ. In particular, individual laminin chains such as laminin-β2, -α4 and -α5 play essential roles in organisation and maintenance of the NMJ. These laminin chains interact together to form three synapse specific laminin heterotrimers; laminin-221 (α2β2γ1), laminin-421 (α4β2γ1) and laminin-521 (α5β2γ1).Laminin-β2 is the common laminin chain found in each of these synapse specific laminin heterotrimers. In-vitro it has been shown to play a key role in the organisation of the presynaptic elements at the NMJ via its interaction and clustering of the N-and P/Q-type voltage-gated calciums (VGCCs). During development of the NMJ, both N-and P/Q-type VGCCs are involved in mediating neurotransmitter release. As the NMJ matures, P/Q-type becomes the dominant channel involved in release while N-type takes on the role of fine-tuning calcium influx. Laminin-α4, on the other hand, ensures proper alignment of presynaptic active zones to postjunctional folds at the NMJ, with its loss resulting in misalignment of these specialisations. Furthermore, this laminin chain has been shown to be involved in the maintenance of the NMJ with the observation of premature ageing features at 6 months of age (6MO) in laminin-α4 deficient mice (lama4 NMJs.In conclusion, this thesis has identified the significant roles laminins-α4 and -β2 play at the NMJ during development, maturation and maintenance. Results suggest that laminin-β2 is not only an important regulator of the presynaptic maturation through the switching of VGCCs and clustering of P/Q-type VGCCs, but also equally important for maturation of the postsynaptic apparatus. Ipropose that laminin-β2 is important for the maturation of each component at the NMJ. The altered responses in transmission properties presented by aged wild-type NMJs which resembled adult lama4 -/-, preceded by altered expression of laminin-α4 chain, strongly suggest that laminin-α4 is not only important for maintaining proper alignment of pre-to postsynaptic NMJ, but also essentially important for maintaining a healthy adult NMJ. Finally, I observed early alterations in expression of laminin-α4 at the NMJs in diseased mouse model of ALS prior to any appearance of neuromotor impairment, suggesting a potential involvement of laminins in NMJ degeneration associated with neuromuscular disorders such as ALS.ii

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

Cited by 33 publications

References 70 publications

A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1α Mutations

A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1α Mutations

Modulation of Smooth Muscle Relaxation by Short and Long Carbon Based Chemicals

The role of synaptic laminins-α4 and -β2 in maturation and maintenance of the neuromuscular synapse

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