Reduced Expression of the Vesicular Acetylcholine Transporter and Neurotransmitter Content Affects Synaptic Vesicle Distribution and Shape in Mouse Neuromuscular Junction

نویسندگان

  • Hermann A. Rodrigues
  • Matheus de C. Fonseca
  • Wallace L. Camargo
  • Patrícia M. A. Lima
  • Patrícia M. Martinelli
  • Lígia A. Naves
  • Vânia F. Prado
  • Marco A. M. Prado
  • Cristina Guatimosim
چکیده

In vertebrates, nerve muscle communication is mediated by the release of the neurotransmitter acetylcholine packed inside synaptic vesicles by a specific vesicular acetylcholine transporter (VAChT). Here we used a mouse model (VAChT KD(HOM)) with 70% reduction in the expression of VAChT to investigate the morphological and functional consequences of a decreased acetylcholine uptake and release in neuromuscular synapses. Upon hypertonic stimulation, VAChT KD(HOM) mice presented a reduction in the amplitude and frequency of miniature endplate potentials, FM 1-43 staining intensity, total number of synaptic vesicles and altered distribution of vesicles within the synaptic terminal. In contrast, under electrical stimulation or no stimulation, VAChT KD(HOM) neuromuscular junctions did not differ from WT on total number of vesicles but showed altered distribution. Additionally, motor nerve terminals in VAChT KD(HOM) exhibited small and flattened synaptic vesicles similar to that observed in WT mice treated with vesamicol that blocks acetylcholine uptake. Based on these results, we propose that decreased VAChT levels affect synaptic vesicle biogenesis and distribution whereas a lower ACh content affects vesicles shape.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Vesicular Monogamy?

Vesicular neurotransmitter transporters package transmitter into the lumen of synaptic vesicles for quantal release. However, the number of transporters that localize to each vesicle is not known. In this issue of Neuron, a study by Daniels et al. using the Drosophila neuromuscular junction and mutations of the vesicular glutamate transporter suggests that one transporter may suffice to fill ea...

متن کامل

Central cholinergic synaptic vesicle loading obeys the set-point model in Drosophila.

Experimental evidence shows that neurotransmitter release, from presynaptic terminals, can be regulated by altering transmitter load per synaptic vesicle (SV) and/or through change in the probability of vesicle release. The vesicular acetylcholine transporter (VAChT) loads acetylcholine into SVs at cholinergic synapses. We investigated how the VAChT affects SV content and release frequency at c...

متن کامل

Aberrant morphology and residual transmitter release at the Munc13-deficient mouse neuromuscular synapse.

In cultured hippocampal neurons, synaptogenesis is largely independent of synaptic transmission, while several accounts in the literature indicate that synaptogenesis at cholinergic neuromuscular junctions in mammals appears to partially depend on synaptic activity. To systematically examine the role of synaptic activity in synaptogenesis at the neuromuscular junction, we investigated neuromusc...

متن کامل

The vesicular acetylcholine transporter is required for neuromuscular development and function.

The vesicular acetylcholine (ACh) transporter (VAChT) mediates ACh storage by synaptic vesicles. However, the VAChT-independent release of ACh is believed to be important during development. Here we generated VAChT knockout mice and tested the physiological relevance of the VAChT-independent release of ACh. Homozygous VAChT knockout mice died shortly after birth, indicating that VAChT-mediated ...

متن کامل

VAAT functionality in cholinergic and dopaminergic neurons

SLC10A4 (Solute carrier family 10 member 4) is a member of the sodium/bile acid cotransporter protein family. Previous studies indicated that this protein is a molecular link between two subpopulations of neurons i.e the monoaminergic and cholinergic. These neural subpopulations are widespread in the central nervous system (CNS) and are involved in most processes of our behaviour related to mot...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2013