Neurotransmission Flashcards
synapse
area where a neuron (cell) communicates with another neuron (or a cell)
electrical synapse
*relies on a current from one cell causing a VOLTAGE CHANGE in the connected cell
*made of gap junctions (connexons make up gap junctions)
*ions and other small molecules move from one cell to another
*present in smooth and cardiac muscle
*can connect: neurons to neurons; glia to glia; neurons to glia
chemical synapses
*transmission is mediated by diffusible chemical transmitters released by the presynaptic cell in response to a change in voltage
*metabotropic and ionotropic receptors are examples of chemical synapses
axosomatic synapses
*between axons and somas
*mostly inhibitory
axoaxonal synapses
*between one axon and another axon
*mostly inhibitory
axodendritic synapses
*between an axon and dendrites
*excitatory or inhibitory
ionotropic receptors
*neurotransmitter binds to and activates receptors that are ligand-gated ion channels
*ex: nicotinic Ach receptors
*in general, faster signaling than metabotropic
metabotropic receptors
*neurotransmitter binds to and activates receptors that act through second messengers
*ex: adrenergic receptors; muscarinic Ach receptors
*in general, slower signaling than ionotropic
sequence of events leading to release of neurotransmitter
1) calcium entry into presynaptic terminal (usually triggered by depolarization and activation of presynaptic voltage-sensitive calcium channels)
2) release of neurotransmitter stored in vesicles
3) vesicles are docked at the presynaptic membrane by tSNARE and vSNARE proteins
4) when calcium levels rise inside the cell, the vesicle is brought in close proximity to the plasma membrane and fusion occurs
5) vesicle contents (neurotransmitters) are released into the synaptic space between the pre and post-synaptic terminals
what determine the response of a neurotransmitter
the RECEPTOR
parathyroid hormone
increases calcium in extracellular fluids by releasing it from bone
where are neurotransmitters synthesized?
in the cytosol of the presynaptic neuron
neurotransmitter: acetylcholine
*neurotransmitter at: NMJ, ANS presynaptic terminals, PANS postsynaptic terminal, some SANS postsynaptic terminals
removal of acetylcholine
acetylcholine esterase breaks down ACh in the synaptic cleft
3 important amino acid neurotransmitters
1) glutamate
2) glycine
3) GABA
neurotransmitter: glutamate
*major EXCITATORY neurotransmitter in CNS ionotropic receptors
*can be excitatory or inhibitory at metabotropic receptors
neurotransmitter: glycine
*inhibitory neurotransmitter
*concentrated in the spinal cord
*mechanism: increase Cl- conductance of the postsynaptic cell membrane (causing hyperpolarization; inhibiting excitabiity)
*all glycine receptors are ionotropic
neurotransmitter: GABA
*inhibitory neurotransmitter
*concentrated in brain and spinal cord
*ionotropic (GABA-A) receptors: increase Cl- conductance of the postsynaptic cell membrane (causing hyperpolarization; inhibiting excitability)
*metabotropic (GABA-B) receptors: increase K+ conductance of the postsynaptic cell membrane (causing hyperpolarization; inhibiting excitability)
removal of glycine
reuptake by the presynaptic neurons and/or surrounding glia
removal of GABA
reuptake by the presynaptic neurons and/or surrounding glia
ammonia and GABA/glutamate/glutamine
*glia convert glutamate + GABA into glutamine (absorbs ammonia)
*important for management of ammonia produced by production of glutamate
examples of biogenic amine neurotransmitters
*catecholamines (dopamine, norepinephrine, epinephrine)
*serotonin
*histamine
what amino acid are the catecholamines (dopamine, NE, and epi) made from?
tyrosine
what amino acid is serotonin made from?
tryptophan
what amino acid is histamine made from?
histidine
most receptors of biogenic amine neurotransmitters are ?
GPCRs; excitatory or inhibitory
dopaminergic neurons & catecholamine synthesis
*secrete dopamine
*presynaptic nerve terminal contains tyrosine hydroxylase and dopa decarboxylase (but not the enzymes further down the pathway)
adrenergic neurons & catecholamine synthesis
*secrete norepinephrine
*presynaptic nerve terminal contains tyrosine hydroxylase and dopa decarboxylase, PLUS dopamine beta-hydroxylase
adrenal medulla & catecholamine synthesis
*secrete epinephrine
*contains the complete enzymatic pathway for catecholamine synthesis (tyrosine hydroxylase, dopa decarboxylase, dopamine beta-hydroxylase, and phenylethanolamine-N-methyltransferase)
neurotransmitter: serotonin
*produced in the serotonergic neurons in brain and GI tract
*precursor to melatonin
removal of serotonin
1) serotonin reuptake into nerve terminal
2) degradation by MAO
removal/degradation of catecholamines
1) MAO (monoamine oxidase): located in presynaptic nerve terminals (on the outer mitochondrial membrane)
2) COMT (catechol-o-methyltransferase): widely distributed and concentrated in the liver, kidney, and GI tract
overall, REUPTAKE AND BREAKDOWN INSIDE THE CELL!
important neuropeptides
*ACTH
*CCK
*substance P / bradykinen
*leptin
neuropeptides - overview
*class of neurotransmitters synthesized as part of larger proteins and cleaved into smaller fragments
*made in soma and must be transported to the synapse (by kinesin)
*most receptors are GPCRs
*use negative feedback
removal of neuropeptides
*slowly cleared by diffusion and breakdown
(tend to be long-acting)
important gas neurtransmitter
nitric oxide
neurotransmitter: nitric oxide
*made by arginine from nitric oxide synthetase
*simple diffusion into smooth muscle cells
*receptor = guanylyl cyclase
*acts to increase cGMP and DILATE smooth muscles (increasing local blood flow)
removal of nitric oxide
rapid breakdown
removal of purine neurotransmitters
breakdown and reuptake
receptor for purine neurotransmitters
ionotropic or metabotropic
receptor for lipid neurotransmitters (endocannabinoids)
metabotropic
removal of lipid neurotransmitters (endocannabinoids)
enzymatic breakdown
excitatory postsynaptic potentials (EPSPs)
depolarizing excitatory potentials are generated by the opening of non-selective cation channels (producing inward, depolarizing current)
inhibitory postsynaptic potentials (IPSPs)
hyperpolarizing inhibitory potentials are generated by ion channels permeable to either K+ or Cl- (producing outward, hyperpolarizing current)
temporal summation
*one of more presynaptic neurons transmit impulses in RAPID-FIRE ORDER
*first impulse produces EPSP, and before it can dissipate, another EPSP is triggered, adding on top of the first impulse
spatial summation
*postsynaptic neuron is stimulated by a LARGE NUMBER OF TERMINALS SIMULTANEOUSLY
*many receptors are activated, each producing EPSPs, which can then add together
why does LOW calcium correlate with HYPER-excitability
the sensitivity of voltage-gated sodium channels is modulated by calcium, so low calcium makes them more sensitive
7 classes of neurotransmitters
1) choline esters (acetylcholine)
2) biogenic amines (dopamine, epi, NE, serotonin, histamine)
3) amino acids (GABA, glutamate, glycine)
4) neuropeptides
5) small gases
6) purines
7) peptides
