synaptic transmission I and II Flashcards
what causes inherited non-syndromic deafness?
50% of cases due to mutation in connexin 26 gene
should be a high K concentration in scala media - with mutation, the high K concentration isn’t maintained - mutation means that the cells in the organi of corti don’t have normal gap junctions and ion gradients can’t be maintained
what are ionotropic channels versus metabotropic channels?
ion = ligand-gated meta = GPCR
what is an excitatory synapse versus an inhibitory synapse?
excitatory will drive membrane potential more positive than the threshold for generating an action potential
inhibition: synapse that keeps the membrane potential from reaching the threshold
what are the major types of ionotropic receptors?
excitatory:
- nicotinic ACh
- glutamine (NMDA and AMPA)
- 5-HT
- purinergic (adenosine and ATP)
inhibitory:
- GABAa
- glycine
(these are both excitatory in the developing brain and in the adult brain after injury)
what are some types of metabotropic receptors?
GABAa metabatropic glutamate 5-HT alpha and beta adrenergic DA muscarinic ACh cannabinoid > 50 for neuropeptides
what are the important snares involved in synaptic docking?
presynaptic membrane:
SNAP25
syntaxin
vesicular:
synaptobrevin
synaptotagmin - snare - Ca sensor
what is the process of docking (molecularly)?
there’s alpha helices associated with the different snare proteins
they lie on top of each other in a parallel arrangement (the vesicle ones over the membrane ones)
zip themselves together => release of lots of energy => fusion of vesicular membrane with plasma membrane
what does NSF do?
promotes parallele assembly of SNARE alpha-helices
also aids in recycling the complex
what do Muncs do?
regulate proper assembly of snares
make sure everything lines up in the right order
what does complexin do?
“clamps” snare assembly
hold everything in place
what does synaptotogmin do?
binds Ca => releases complexin clamp, facilitates C2 region insertion into presynaptic membrane
how do botulinum and tetanus toxins work?
cleave SNAREs => blocking synaptic vesicle exocytosis
what is lambert eaton syndrome?
genetic disorder where autoantibodies against P/Q Ca channels are made
get deficiency in release of NT
see improvement if you give them something that blocks K channels in synapse => increased depolarization because you’ll get an action potential thats longer => gives Ca channels more time open and more Ca can get into cell
what is the ACh receptor permeable to?
Na and K K goes out Na goes in slightly more permeable to Na than K drive membrane potential to 0 = reversal potential - beyond threshold for generating action potential
what happens if you block acetylcholineesterase (AChE)?
ACh receptors desensitize - get muscle weakness and fasciculations, difficulty in breathing, tracycardia
can be due to organophosphates (pesticides)
(AChE is what breaks down ACh in the synaptic cleft)
what does succinylcholine do?
resistant to acetylcholinesterase
binds to ACh binding site with high affinity
promotes AChR desensitization and can be used to induce clinical paralysis (ie for intubations)
what is myasthenia gravis? what causes it? how do you treat it?
disease in which autoantiboides against AChR are produced - don’t have as many receptors available => membranes simplify
get ptosis, other muscle weaknesses
inhibit AChE to treat
what is the quantal hypothesis?
determines efficacy of synaptic transmission m = n * p m = mean quantal content n = number of vesicles p = probability of release
this basically says that each vesicle will change the voltage by about the same amount - each vesicle holds a “quantal” amount of NT
what makes gap junctions?
6 connexins make a connexon = the channel
the actual gap junction has hundreds of these connexons clustered together
what do nicotinic Ach receptors mediate?
fast EPSPs in peripheral neurons
presynatpic modulation in CNS = major action o fo nicotine in CNS
nicotine is agonist - activation of AChR depolarizes presynaptic terminal and allows Ca to enter through both the AChR and by opening the Ca channels => enhanced NT release
what is the effect of nicotine in the CNS?
binds to AChR
depolarizes terminal and allows Ca to enter through the receptor
therefore enhances activity of dopaminergic neurons by increasing presynaptic NT release from excitatory glutamatergic inputs and decreasing presynaptic NT release from inhibitory GABAergic inputs (have different types of AChR)
