Exam 1: Slide 4 Flashcards
Otto Loewi
In 1926, this German physiologist proved that electrical signals can cause neurotransmitter release
What did Otto Loewi’s experiment entail?
1) two frog hearts were bathed in fluid
2) The first heart was electrically stimulated, which caused slowing of the heart
3) The fluid surrounding the stimulated heart was then transferred to the fluid surrounding the second heart
4) Just being bathed in the fluid of the first heart caused the second heart to slow as well
5) Because the second heart responded by slowing down, even though it was not electrically stimulated, Loewi concluded that a chemical must have been released from the first heart
6) The chemical was later identified as the neurotransmitter acetylcholine
Three Primary Neurotransmitter Criteria
- The substance must be present within the presynaptic neuron
- The substance must be released in response to presynaptic depolarization and the release must be calcium dependent
- Specific receptors for the substance must be present on the postsynaptic cell
How does neurotransmitter release occur?
Work in the 1970s demonstrated that neurotransmitter release occurs as a result of vesicles fusing with the presynaptic membrane and releasing their neurotransmitter contents
The critical step in vesicular fusion is
the influx of calcium via the voltage gated calcium channels
Evidence for Calcium
- Artificially injecting calcium into the presynaptic terminal causes neurotransmitter release
- Preventing internal calcium increase during an action potential prevents neurotransmitter release
The basic process of vesicular fusion is as follows: (1)
- The protein synapsin is present on vesicles and binds to the cytoskeleton of the neuron
The basic process of vesicular fusion is as follows: (2)
- When calcium enters the cells following an action potential, proteins called Ca2+/calmodulin-dependent protein kinase type II (CaMKII) bind this calcium and cause synapsin to release from the vesicle
The basic process of vesicular fusion is as follows: (3)
- Once synapsin releases, the vesicle can move to the presynaptic membrane at the synapse
The basic process of vesicular fusion is as follows: (4)
- The two types of protein classes involved in vesicular fusion are SNAREs and SNAPs. Both work to prime the vesicle for fusion. They ensure the vesicle is in the proper position to fuse i.e. “docked”
The basic process of vesicular fusion is as follows: (5)
- Synaptotagmin is located on the vesicle and senses calcium influx as well. It causes the docked vesicle to fuse with the membrane
There are two broad categories of neurotransmitter (NT):
- small molecule and peptides
- Neurons can release one type or both types of neurotransmitters
Which frequency releases which type of NT
in neurons that release both, low - frequency activity causes release of small molecule NTs and high - frequency causes release of peptides
Where are the different types of NT made?
The NTs are made differently as well: small molecule in the axon terminals and peptides in the cell body
Small molecule neurotransmitter synthesis and transport:
- Synthesis occurs locally within axon terminals
- The enzymes needed to synthesize the neurotransmitters are sent from the cell body to the axon terminals by slow axonal transport
- The neurotransmitter is then loaded into vesicles at the terminal—the vesicles are visually clear (i.e. small clear-core vesicles)