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Flashcards in Holmes 4 Deck (23):

Synaptic transmission...two types, what are they? how do they differ?

Electrical synapse: current passes directly to the postsynaptic cell, depolarizing it
-no delay and is BIDIRECTIONAL

Chemical synapse: current results in release of transmitters that act on postsynaptic membrane to open ion channels
-has gap delay and is UNIDIRECTIONAL


What structure connects two cells in an electrical synapse? what disease are associated with defects?

-connected by gap junction (pair of hemichannels)
-6 subunits called connexins (12 total)

defect: deafness, neuropathies (charcot-marie-tooth-disease), cataracts
-cancer; gap junction is a tumor suppressor gene


T/F electrical transmission is NOT graded and occurs when the currents in the presynaptic cell are below the threshold for an AP

False, it IS graded (does not need AP to transmit information) and can even occur when the currents in the presynaptic cell are below the threshold for an AP


Gap junctions are important for cardiac muscles. Why?

Signals pass efficiently through gap junctions. Allows cardiomyocytes to contract together (tandem). Problem is with ectopic pacemakers (pacemaking activity that arises elsewhere in the heart; competes with normal pacemaking)


What stimulates neurotransmitter release in chemical synapses?

Ca2+ uptake, remember there is delay in chemical synapses

-human neuromuscular muscles don't have excitatory and inhibitory inputs into muscle (just excitatory)


What is the advantage of electrical synapse? Chemical?

Electrical synpase: has speed and reliability
Chemical synapse: can mediate excitation or inhibition, greater plasticity


What are the principal inhibitory neurotransmitters of the human nervous system? Excitatory?

GABA and glycine
-glutamate is the excitatory neurotransmitter
-all are of the amino acids class

-acetylcholine (Ach) is also very important (depends, excites nicotinic receptors)


-oxytocin is for maternal fxns


What is the diff between neuropeptide neurotransmitters and those of other classes?

Neuropeptide neurotransmitters are larger and cost more energy to produce


What is the major CNS excitatory neurotransmitter? Describe it.

Glutamate (amino acids)
-ionotropic receptors: AMPA, NMDA, Kainate
-acts on GPCRs mGluR receptor (ionotropic)


Describe histamine

Excitatory or inhibitory
-Acts on H1-4 receptors and GPCRs (metabotropic)
H1: modulate circadian cycle
H3: inhibits release of other neutrotransmitters (Ach, dopamine, etc.)


Major inhibitory neurotransmitters? Describe

GABA: made from glutamate (amino acids)
-acts on GABA receptors
GABAa: Cl- channels (ionotropic)
GABAb: K+ channel activation (causes hyperpolarization) using G protein (GPCR) (metabotropic)

Glycine: acts on glycine receptors (amino acids)
GlyR: Cl- channel (ionotropic)


Acetylcholine? Serotonin?

Acetylcholine (excitatory in NMJ) (choline esters)
nicotinic and muscarinic receptors (iono/metabotropic)
-neuromuscular junction exclusive
-acts on parasymp nervous system, sympathetic nervous system and adrenal medulla

Serotonin (biogenic amine)
-derived from typtophan
-excitatory and inhibitory
-acts on serotonin receptors, metabo/ionotropic
-acts on brain/GI tract


Dopamine? Norepinephrine? Epinephrine?

Excitatory and inhibitory; derived from tyrosine..class of catecholamines

dopamine: inhibits release of prolactin (biogenic amine)

norepinephrine: fight or flight (biogenic amine)
-adrenergic neurons

epinephrine: fight or flight (biogenic amine)
-adrenergic neurons
-released by adrenal medulla


describe process of making neuropeptide

mRNA -> pre-prohormone -> prohormone (in golgi) -> vesicles -> synaptical terminal

neuropeptide into neurohormone or neuromodulator

neurohormone: secreted into bloodstream distant sites

neuromodulator in presynaptic cell: regulate neurotransmitter release

neuromodulator in postsynaptic cell: cosecreted with other neurotransmitters


Describe NO

NO - nitric oxide
-freely diffusing gas
-does not bind to membrane receptors
-covalently modifies effectors


Describe purines (ATP) as a neurotransmitter

-ATP is released with noradrenaline (NA) and neuropeptide Y (NPY) from perivascular sympathetic nerves
-evoke smooth muscle contraction
-important for immune system


Describe parkinson's disease and causes.

causes are genetic and environmental
-derivatives of L-Dopa (dopamine derivative) are used to tread PD to compensate for loss of dopaminergic neurons in the SUBSTANTIA NIGRA


What is reserpine toxicity?

-Reserpine was drug to treat hypertension
-caused depression though because of irreversible blocking of vesicular monoamine transporter (VMAT)


Describe calcium release for synapses.

1) open voltage-gated Cav channel
2) Ca2+ rises near presynaptic membrane
3) triggers fusion of presynaptic vesicles loaded with transmitters

fxn similarly to Nav channels
-slower inactivation than Nav
-located near vesicle docking zones
-during AP, Ca2+ concentration can rise more than 1000x


What disorder is associated with malfunctioning presynaptic release at NMJ?

Lambert-Eaton myasthenic syndrome
-LEMS is an autoimmune disorder
-antibodies against voltage-gated calcium channels in presynaptic terminal at NMJ
-treatment of malignancy can treat LEMS


What are some proteins involved in synaptic vesicle fusion?

SNAP, SNARE (zipper model), VAMP, Synaptotagmin (calcium sensor)


What is botox?

Botox uses botulinum toxin to cleave SNARE proteins (zipper)


What happens to the empty vesicles at presynaptic cleft?

Classical pathway: excess membrane retrieved by clathrin-coated pits (not found at active zone)

Kiss and run pathway: vesicle does not completely integrate with PM, neurotransmitter released through fusion pore

Bulk endocytosis pathway: excess membrane reenter the terminal by budding from uncoated pits (formed at active zone)