Synapses and Neurotransmitters Physiology

Outline the process of chemical synaptic transmission

Neurotransmitters are released from axon terminals, diffuse across the synapse, bind to receptors on postsynaptic cells and elicit a response

Chemical vs electrical synapses in terms of PSP and directionality

Chemical are excitatory or inhibitory and unidirectional

Electrical is bidirectional and only excitatory

What are the primary components of the neuromuscular junction

Presynaptic efferent motor neuron, synaptic membranes, synapse, neurotransmitter (acetylcholine ACh), nicotine acetylcholine receptor on the Postsynaptic muscle cell/myocyte

Motor unit

Consists of a motor neuron plus all of the muscle cells it innervates. Each muscle cell only receives signals from one neuron

What enzyme synthesizes ACh and where

Choline acetyltransferase (ChAT). ChAT is synthesized in cell body and transported down the axon, ACh synthesis occurs in axon terminal from acetyl CoA and choline

How do synaptic vesicles mediate the storage and release of ACh

Mediated by Vgated Ca channels which open to let calcium in which binds to synaptotagmin.

Synaptotagmin and Synaptovrevin are associated with the vessicle. SNAP-25 and syntax are in the membrane and hold the vessicle close

Structure and function of nicotinic acetylcholine receptors

Bind ACh or nicotine. Has two binding sites and activation requires binding of both. It is a ligand gated ion channel permeable to small cations like sodium potassium and calcium. Stimulates depolarization and EPSPs

Structure and function of junctional folds

Invaginations in the myocyte membrane. Increase the surface area for expression of AChRs. Density of receptors are at the portion closest to presynaptic membrane (mouth)

Sequence of events in neuromuscular junction signaling

AP travels down axon, reaches Vgated Ca channels in axon terminal, influx of calcium binds synaptogamin, this flexes the proteins holding the vessicle and puts it in contact with the membrane, Exocytosis of ACh occurs, it diffuses across the synapse binding to nicotinic AChR, once two have bound to the receptor the ligand gated ion channel opens allowing influx of sodium and calcium and an efflux of potassium, this is a brief interaction and ACh is inactivated by Acetylcholinesterase (AChE) which breaks it down into acetic acid and choline. Acetic acid diffuses away and choline is recycled back to the presynaptic membrane by choline transport proteins

Describe the mechanism responsible for ACh inactivation

ACh is inactivated by Acetylcholinesterase (AChE) which breaks it down into acetic acid and choline. Acetic acid diffuses away and choline is recycled back to the presynaptic membrane by choline transport proteins

What is the difference between neuromuscular junctions and neuron-neuron junctions including neurotransmitter utilized, location of postynaptic membrane, and mechanisms with neurotransmitter inactivation

Neurotransmitters very widely in neuron to neuron, and neurotransmitters are not always relasesed in the cleft like neuromuscular,

Three methods of down regulation in neuron-neuron neurotransmitters

-Enzymatic degradation (slow)

-Transporter-mediated reuptake

-Simple diffusion of neurotransmitter

Post synaptic membranes in n-n is in one of three spots

- Dendrties, cell body, or axon terminals

How do alterations in AP generation or propagation affect neurotransmitter release

Increased AP frequency = increased neuro transmitter release

Increased AP frequency can also stimulate the release of additional type of neurotransmitter

Define receptor desensitization, down-regulation, hypersensitization, and up-regulation

Desensitization= biding affinity of the receptor for the ligand is reduced

Hypersensitization= binding affinity of the receptor for the ligand is increased

Down regulation= number of receptors expressed by cell is reduced

Up regulation= number of receptors expressed by cell is increased

How do ligand availability affect receptor expression and affinity

Prolonged or excessive ligand presence leads to downregulation and/pr desensitization or receptors

Reduced ligand presence leads to upregulation and/or hypersensitization of receptors

Ionotropic vs metabotropic receptors

Ionotropic= directly opening an ion channel (ligand gated ion channel). Quicke response and deactivation

Metabotropic= stimulate or inhibit intracellular biochemical cascades after ligand binding. Membrane potential indirectly mediated. Slow but longe response

Ionotropic receptor examples

nicotinic ACh receptor- binds ACh allowing Na K and C to pass through

NMDA receptor- simultaneously binds glutamate and glycine. Once both are bond AND membrane depolarization occurs it becomes permeable to small cations like Na K and Ca and stimulate depolarization

GABA-A receptor- primarily in CNS, binds GABA, become permeable to Cl and therefor hyperpolarization/IPSP

Metabotropic receptors examples

Muscarnic acetylcholine receptor- GPCR , there are 5 different kinds

-M1 are expressed in CNS and autonomic nervous system, coupled to Gq

Beta-adrenergic receptors- GPCR, bind norepinephrine, epinephrine, or several related exogenous compounds. Expressed in CNS. Coupled to Gs