synaptic transmission I and II

Question 1

what causes inherited non-syndromic deafness?

Answer 1

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

Question 2

what are ionotropic channels versus metabotropic channels?

Answer 2

ion = ligand-gated
meta = GPCR

Question 3

what is an excitatory synapse versus an inhibitory synapse?

Answer 3

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

Question 4

what are the major types of ionotropic receptors?

Answer 4

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)

Question 5

what are some types of metabotropic receptors?

Answer 5

GABAa 
metabatropic glutamate
5-HT
alpha and beta adrenergic
DA
muscarinic ACh
cannabinoid
> 50 for neuropeptides

Question 6

what are the important snares involved in synaptic docking?

Answer 6

presynaptic membrane:
SNAP25
syntaxin

vesicular:
synaptobrevin
synaptotagmin - snare - Ca sensor

Question 7

what is the process of docking (molecularly)?

Answer 7

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

Question 8

what does NSF do?

Answer 8

promotes parallele assembly of SNARE alpha-helices

also aids in recycling the complex

Question 9

what do Muncs do?

Answer 9

regulate proper assembly of snares

make sure everything lines up in the right order

Question 10

what does complexin do?

Answer 10

“clamps” snare assembly

hold everything in place

Question 11

what does synaptotogmin do?

Answer 11

binds Ca => releases complexin clamp, facilitates C2 region insertion into presynaptic membrane

Question 12

how do botulinum and tetanus toxins work?

Answer 12

cleave SNAREs => blocking synaptic vesicle exocytosis

Question 13

what is lambert eaton syndrome?

Answer 13

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

Question 14

what is the ACh receptor permeable to?

Answer 14

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

Question 15

what happens if you block acetylcholineesterase (AChE)?

Answer 15

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)

Question 16

what does succinylcholine do?

Answer 16

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)

Question 17

what is myasthenia gravis? what causes it? how do you treat it?

Answer 17

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

Question 18

what is the quantal hypothesis?

Answer 18

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

Question 19

what makes gap junctions?

Answer 19

6 connexins make a connexon = the channel

the actual gap junction has hundreds of these connexons clustered together

Question 20

what do nicotinic Ach receptors mediate?

Answer 20

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

Question 21

what is the effect of nicotine in the CNS?

Answer 21

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)