College of Alameda Human Physiology

Synaptic Transmission Neurotransmitters Regulation of chemically gated channels

Synapse
Is a functional connection between two neurons (presynaptic & postsynaptic) There are two forms of synpses
chemical & electrical synapses (through gap junctions)

Chemical synapse useneurotransmitters (NT) Electricals are rare in NS

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Chemical Synapse
Vesicles fuse with bouton membrane; release NT by exocytosis Amount of NT released depends upon frequency of APs
1. 2. 3. 4. Ca activates a regulatory protein, calmodulin calmodulin activates an enzyme called protein kinase Pr. Kinase phosphorylates synapsins in the membrane of the synaptic vesicles Synapsins aid the fusion of synaptic vesicles with the plasma membrane

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Synaptic Transmission
NTs may depolarize or hyperpolarize the second neuron.
Depolarizing: cause EPSPs (excitatory postsynaptic potentials) Hyperpolarizing: cause IPSPs (inhibitory postsynaptic potentials)

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Depolarization/Hyperpolarization

EPSPs
Synaptic potentials are graded potentials. Therefore synaptic potentials: can add together, or summate fade quickly over time & distance have no threshold have no refractory period

1. 2. 3. 4.

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Synaptic Summation
Spatial summation takes place when many EPSPs (up to thousands) from different synapses occur in one postsynaptic cell at same time Temporal summation occurs when EPSPs that occur closely in time can sum before they fade

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Synaptic Inhibition-IPSP

IPSP is caused by NTs that can hyperpolarize the second neruon:

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Presynaptic inhibition:
Occurs when neuron #1 synapses onto axon of neuron #2 inhibiting release of its NT The GABA released from N#1 decrease the entry of Ca into the N#2 and thus decrease the release of NT from N#2 This may involve increase conductance of either Cl or K ions. In practice: Norepinephrine is know to act presynaptically on 2 receptors to inhibit further transmitter release.

Neurotransmitters
I. II. Acetylcholine (ACh) Biogenic amines (monoamines)

III. Amino acids IV. Peptides V. Novel messengers: ATP and dissolved gases NO and CO

ACh
Has two subtype of the receptors
nicotinic ACh receptor muscarinic ACh receptor

At Somatic motor nerve ending (at NMJ), the receptor is nicotinic and Ach is excitatory At autonomic nerve ending,
If the receptor is nicotinic ACh is excitatory If the receptor is muscarinic ACh is inhibitory

Regulation of Chemically gated channels

NT can open ion channels through two different mechanism. 1. Ligand-operated channels
opens when ligand (NT) binds to receptors

2. G-protein-operated channels

Nicotinic ACh Channel

Ion channel runs through receptor Opens when 2 AChs bind Permits diffusion of Na+ and K+ Inward flow of Na+ dominates EPSP The simultaneous outward diffusion of K prevents the depolarization from overshooting 0mv.
the membrane polarity does not reverse in an EPSP
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G Protein-Operated Channels
Receptor is not part of the ion channel
Activates channel indirectly through G-proteins

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Muscarinic ACh Channel

Binding of 1 ACh activates G-protein cascade The subunit dissociates Depending on specific case, either the or complex diffuse through the membrane to binds to a K channel; causing the channel to open or close Shortly after the or complex dissociate from the channel and moves back to its previous position this cause the K channel close or open

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Ex. For Muscarinic ACh Channel

In the smooth muscles of the stomach, subunit binds to the K channels and close it the outward diffusion of the K is reduced depolarization

How to remove Ach?

1. Acetylcholinesterase (AChE): Located in synaptic cleft

2. astrocytes 3. presynaptic reuptake 4. ACh Diffuse from the synaptic cleft

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In practice
The drug curare compete for nicotinic receptors on postsynaptic muscle fibers (motor end plate/NMJ) prevents EPSP. This drug is used in surgery as a muscle relaxant.

Biogenic Amines
Include:
Catecholamines:
Dopa Dopamine Norepinephrine (NE) and Epinephrine

Indolamines:
Serotonin Histamine

Distributed in the brain

NE
Some neurons in CNS These neurons seem to be involved in general behavioral arousal In practice Amphetamine which stimulate pathways in which NE is used as a neurotransmitter, cause mental arousal

Norepinephrine

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How to remove NE?

1. Presynaptic reuptake (mostly) breakdown by monoamine oxidase (MAO) 2. In postsynaptic neuron catecholamines can be breakdown by catechol-Omethyltransferase (COMT)
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Dopamine
Involved in
motor control emotional reward

Neurons which secrete dopamine are in midbrain Axons of these neurons are found into two systems
Nigrostriatal dopamine system Mesolimbic dopamine system

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Bridge to Anatomy

Nigrostriatal system: cell bodies of the neurons are located in substantial nigra (a part of midbrain) the axons reach another nucleus called corpus striatum Mesolimbic system: The neurons starts from midbrain and reach to forebrain (part of limbic system). These system is involved in behavior and reward

In practice
1. Parkinsons disease is caused by degeneration of the dopaminergic neurons in the substantial nigra 2. Schizophrenia treated by anti-dopamine drugs (neuroleptics) cause side effects resembling Parkinsons disease 3. Alcohol, amphetamine, cocaine, marijuana, morphine and nicotine promote the activity of dopaminergic neurons that arise in the midbrain and terminate in the nucleus accumbens of the forebrain

Serotonin (5-hydroxytryptamine, 5HT)

Neurons located along the midline of the brain stem, raphe nuclei, use serotonin as a NT Has a diverse functions due to large number of subtypes of serotonin receptors (over a dozen)
relieve depression treat anxiety reduce appetite relieve migraine Regulate cerebral circulation

LSD, a hallucinogen, is structurally similar

Histamine
Is present in neurons of the hypothalamus

Amino Acids
Found only in the CNS Excitatory NTs
Glutamic acid:
the most abundant fast excitatory NT At chemical synapses, glutamate is stored in vesicles. Glutamate receptors, such as the NMDA receptor is found in the post-synaptic cell. It is involved in cognitive functions like learning and memory

Aspartic acid

Inhibitory NT
Glycine: In spinal cord. Opens Cl- channels. GABA: the most common inhibitory NT in brain, opens Clchannels

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Peptides
Often called neuropeptide
Substance P: mediator of pain signals Beta endorphin Dynorphin Enkephalins Neuropeptide Y(NPY): most common neuropeptide
Powerful stimulator of appetite (leptin appears to act, at least in part, by inhibiting NPY synthesis and release in the hypothalamus)

Gut-brain peptides:
Somatostatin Cholecystokinin: give feeling of satiety in the brain

NO & CO
are gaseous NTs
Act through cGMP second messenger system

NO
Is not packaged in the vesicle. It is synthesized as it is needed Is inhibitory NT in CNS and enteric nervous system causes smooth muscle relaxation
Viagra increases NO

within macrophages help to kill bacteria Is involved in learning and memory

CO
Certain neurons including one in cerebellum and in olfactory epithelium produce CO