Synapses Flashcards
what are the two major categories of neurotransmitters
small- biogenic amines, glutamate, GABA, AcH
large/neurohormones- opioids, cannabinoids, vasopressin, oxytocin, GnRH
two major receptor classes
ionotropic- ligand gated channels w/ ion channel at core.. amino acids line the pore that confers ion selectivity. operate in milliseconds. ligand binding causes a confirmational change. do not requre ATP
metabotropic- g-coupled receptors w/o ion channel. ligand gating activates second messengers that affect neighboring ion channels. produce slower effects than ionotropic
major excitatory receptors
nicotinic AcH (skeletal and neuronal)
glutatamate- (NMDA, AMPA, Kainate)
purinergic- (adenosine and ATP)
major inhibitory receptors
GABA type A (major fast inhibitor in the brain)
glycine- (major fast inhibitor in spinal cord)
define NT excitation
drive membrane potential towards a value that is more depolarized than the threshold potential for an AP
what is the NT/receptor combination at neuro muscular junctions
AcH/ nicotinic AcH receptors
safety factor
each AP in the presynaptic cell gives rise to an AP in the post synpatic cells
how are the safety factors in the musculature different than those in the CNS?
in the musculature, a presynaptic AP = postsynaptic AP
in CNS, presynaptic APs release very little NT
active zones
found in the presynaptic terminal of the nmj, it is the combination of vesicles docked to the cytoskeleton adjacent to voltage dependent Ca channels. when Ca enters, it will trigger fusion and exocytosis of AcH from within the vesicles
describe the Ca influx in the presynaptic vesicle
huge driving potential, nernst potential is +100. rapidly increases free {Ca}, but only near the membrane. this allows it to be quickly buffered back down.
synaptic delay
time it takes for arrival of AP in presynpatic terminal until influx of postsynpatic current
SNARE
proteins on the vesicle and membrane that are responsible for the proper fusion and exocytosis of NTs. when in contact, they undergo a confirmational change in the a-helicies and zipper together, releasing energy that feeds fusion of the vesicles
synaptotagmin
calcium sensor in the SNARE complex. Ca binding releases binding proteins from the complex and allows the conformational changes that promote membrane/vesicle fusino to occur
quantum
release of NT occurs in discrete packets because of their vesicle-mediated release mechanism
botulinum and tetanus toxins
target SNARE proteins involved in vesicle release
botox is targeted to acidic vesicles, where the pH releases the light chain into the cytoplasm. it can then cleave SNAREs
tetanus si retrogradely transmitted through a-motorneurons to secondary inhibitor interneurons
nicotinic AcH R
found at nmjs, ionotropic
permeable to both Na and K. Na flows in, K flows out. drives potential to 0 mV. selectivity slightly favors Na
reversal potential
“equilibrium potential” in ionotropic pores w/ 2 ions. movement across the reversal potential causes flux to reverse direction
what is the action of any NT at an ionotropic receptor
drive the membrane potential towards the reversal potential
what are the 2 ways neurons can alter their efficacy?
efficacy= strength
1 altering # of vesicles released
2 altering probability that any vesicle will be released
given by equation
mean quantal content = number of vesicles x probability of vesicle being released
why are nmj synapses so effective
each AP releases lots of AcH
and the postsynaptic fibers are specialized (lots of receptors found at the top of postsynpatic folds) to optimize the ACh
lambert eaton syndrome
autoimmune disorder where Abs directed at presynaptic VDCC in presynaptic motorneurons and cholinergic neurons in the ANS. results in defectuve synaptic transmission
manifested by muscle weakness, fatigue, difficulty walking, speech and swallowing difficulties
treated w/ voltage dependent K blocking drugs
post synaptic nmj specialization
clusters of AChRs at the tops of membrane folds
high density voltage dependent Na channels in the troughs which trigger excitation/contraction
folds form a funnel that directs free ACh. this funnel has a basal lamina w/ AChE embedded, which breaks down free ACh
AChE
breaks down ACh. binds at 2 sites and releases free choline
ligand gated desensitization
if ligand remains bound for an extended period of time, then the receptor will undergo a conformational change that results in a non-conducting state
