Lecture 11 Flashcards
(26 cards)
what occurs in the activation of the post synaptic membrane
- ACh bind to receptor once Na+ and K+ flow down gradient, but since inside is negative Na+ flux in is greater and K+ is pulled back in
- the end result is a local depolarization or EPP
what happens to magnitude of EPP as it flows away from NMJ
it reduces
What channels does an EPP open
Na+ and K+ channels, sequentially, Na+ first then K+
what are the ways synaptic transmission can be terminated
- uptake or reuptake of NT
- enzymatic degradation
- ligand/receptor complex internalization
what happens in uptake or reuptake of NT
- in uptake, NT binds to receptors on glial cells where it may be degraded and disposed
- inreuptake, NT binds to receptors on pre synaptic neuron from which it was released where it is repackaged into new vesicles
what happens in enzymatic degradation
enzymes specific to that NT cleave NT into pieces, eliminating its binding ability. the pieces get taken back up into presynaptic terminal for reuse
what happens in ligand/receptor complex internalization
it is internalized into post synaptic cell which can lead to metabotropic responses altering cell function in a long term manner
what is myasthenia gravis
an autoimmune disease where the body makes antibodies that attack their own ACh receptors. thus normal safety factor is lost, EPP is very small, and fails to activate AP and muscle contraction
what are symptoms of myasthenia gravis
- fatigue from need for repeated signaling by nervous system to bring muscle to threshold
- weakness from inability to activate muscle contraction
what are treatments for myasthenia gravis
immunosuppressants to decrease the number of antibodies, most relevant us tif Act esterase inhibitor since AChE can’t cleave Ach there is more Ach available to bind, increasing possibility for EPPs of sufficient magnitude to activate Na+ and K+ channels to initiate AP
what are endocannabinoids and what do they do
-endogenous substances synthesized from plasma membrane of post synaptic cell, traveling back across synapse they bind to GPCRs which inhibit release of NT from the presynaptic neuron.
where are endocannabinoids involved
limbic and hypothalamus
what does adenosine do
can bind to GPCRs on the presynaptic membrane to decrease NT release from that membrane
what do BDNF and NT4/5 do at the NMJ
bind to TRK receptors and activate the ras-MAPK pathway
what are the short term effects of the ras-MAPK pathway
- phosphorylate exocytosis proteins such as synapse or synaptotagmin which helps mobilize larger vesicles containing neurotrophic substances
- this increases synaptic communication and increases depolarization and local release of Ca2+ from SR
what are the long term effects of the ras-MAPK pathway
- TFs transported back to neuronal soma for modulation of protein synthesis or transcription of new proteins
- increased production of NT, vesicles, and microtubules for transport
- improve NMJ structure with more integrated or altered shape
what does calcium do at the NMJ
- APs arrive at terminal bouton, activate Ca2+ channels allowing influx of Ca2+ and localized increase in intracellular calcium concentration
- post synaptic activated of muscle leads to SR release of CA for contraction
what does calcium do at muscle
-release of Ca from SR and/or stretch activated opening of Ca channels in sarcolemma due to contraction lead to increased intramuscular Ca
what does calmodulin do
has no enzymatic properties but once calcium binds it undergoes conformational change that enables it to act as a dock for proteins
what does CAMKinase do in synaptic structures
mediates effects of BDNF and NF4/5
what does vesicular release and fusion rely on
Ca2+ influx
what activates fast fiber types
high frequency of calcium
what is the effect of high frequency activation
could alter protein synthesis in muscle by up regulation genes in MAPK path or myosin heavy chain isoforms by turning on transcription for those isoforms
what happens at the presynaptic terminal when Ca is released
vesicular release of Ach and peptide trophic factors
