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Neuromuscular synaptic function depends
critically on the precise spatial apposition of
presynaptic motor neuron acetylcholine release
sites with high-density clusters of acetylcholine
receptors (AChRs) in the postsynaptic muscle
fiber membrane. During neuromuscular
synaptogenesis, AChRs are clustered before
innervation, prepatterning a central muscle
region where synapses will later be established.
Motor neuron signals refine the muscle prepattern
by clustering AChRs beneath terminals and
dispersing uninnervated clusters so that AChRs
become localized to, and are stably maintained
at, nascent synapses. Over the last 15 years,
work from a number of groups has uncovered the
basic signaling mechanisms that underlie these
events. Muscle-specific kinase (MuSK), a receptor
tyrosine kinase expressed by postsynaptic muscle
fibers, is essential for the formation of
aneural, prepatterned AChR clusters as well as
for the formation and maintenance of later,
innervated AChR clusters. The presynaptically
released proteoglycan agrin is now more fully
understood to be important as an
anti-declustering, AChR cluster maintenance
factor. A role for the neurotransmitter ACh as a
cluster dispersion factor for noninnervated AChR
clusters has also recently come to be appreciated.
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Once neural cell fate is specified and neuron
precursors have migrated to the appropriate
regions, they extend polarized projections that
become their axons and dendrites. The axonal
processes can extend long distances, navigating
complex cellular environments before reaching
their postsynaptic partner. This guidance is
mediated through the growth cone, a specialized
sensing device at the tip of the outgrowing axon.
Growth cones express a series of guidance
receptors that are capable of sensing a variety
of long-range (diffusible) and short-range
(surface-bound) guidance cues. These guidance
cues, which can be attractive or repulsive, are
secreted by guidepost cells and intermediate
targets. The spatial and temporal presence of the
guidance cues, combined with the expression of
the receptors in the growth cone, enables the
axon to navigate through the labyrinth that is
the developing nervous system to reach its
target. Upon reaching and contacting its target,
the axon transforms into a presynaptic
specialization capable of transducing synaptic
signals to the postsynaptic target.
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Il neurone utilizza per condurre informazioni
rapidamente per lunga distanze segnali elettrici
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Differente permeabilità della membrana alle
differenti specie ioniche
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Il neurone utilizza per condurre informazioni
rapidamente per lunga distanze segnali elettrici
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• I CANALI IONICI sono immersi nella matrice della
  membrana plasmatica. Essi possono essere
• 1. PASSIVI sono sempre aperti e non influenzati
  dal potenziale di membrana. Il loro ruolo è di
  mantenere stabile il potenziale di riposo
• 2. ATTIVI si aprono solo in risposta a
  determinati stimoli (chimici o elettrici o di
  altra natura fisica). Concorrono alla generazione
  di potenziali che modificano il potenziale di
  riposo di una cellula, inducendo la

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• Difficoltà
• Studi strutturali
• Studi funzionali

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Potassium Channel Structure

• The a subunit is formed from 6 transmembrane
  segments and is associated with a regulatory b
  subunit.
• Four a subunits form the pore.