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)
NO NEUROTRANSMITTER IS INTRINSICALLY INHIBITORY OR EXCITATORY
-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)
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 (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)
epinephrine: fight or flight (biogenic amine)
-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
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)