Neurotransmitter Release and Calcium Ions

Synaptic Transmission

• Synaptic transmission involves chemical and electrical transmission.
• Morphological studies examine the structure of synapses.
• Physiological studies investigate the function of synapses.

Neurotransmitters

• Acetylcholine (ACh), amino acids, amines, and peptides are neurotransmitters.
• ACh, amino acids (like glutamate and GABA), amines (like dopamine and serotonin), and peptides are neurotransmitters.
• Neurotransmitters' uptake and termination processes are crucial.
• Pharmacology research studies the effects of drugs on neurotransmitters.
• Neurotransmitters like acetylcholine (ACh) are crucial for neuromuscular activity.
• Botulinum toxin and tetanus toxin affect SNARE proteins, which affect synaptic transmission.
• Neurotransmitters are released by exocytosis.
• Specific receptors for neurotransmitters, like the nicotinic ACh receptor, are targeted by various toxins.

Chemical Synapses

• Chemical synapses are common and use neurotransmitters to transmit signals across a 200 nm gap between the presynaptic and postsynaptic neurons.
• Chemical synapses rely on chemical neurotransmitters to signal across the synapses.
• Chemical synapses have receptors for these neurotransmitters on the postsynaptic neuron.
• Ligand-gated ion channels or ionotropic receptors are postsynaptic receptors involved in chemical signaling.
• The neuromuscular junction (NMJ) uses acetylcholine (ACh) as a neurotransmitter.

Electrical Synapses

• Electrical synapses are rare and allow direct electrical signal flow for fast transmission across a 20-nanometer gap.
• Electrical synapses use connexons.
• Connexons are protein channels that allow direct electrical signal transmission.

Synaptic Morphology - Neuromuscular Junction (NMJ)

• Immunochemistry methods are used to identify pre- and post-synaptic membrane proteins.
• The neuromuscular junction (NMJ) is a synapse between a motor neuron and a muscle fiber.
• The NMJ involves pre-synaptic axon terminals and post-synaptic muscle fiber structures.
• Spider and cobra toxins affect pre- and post-synaptic receptor proteins at the NMJ respectively.

Morphological Evidence for Exocytosis During Neurotransmission

• TEM (transmission electron microscopy) and SEM (scanning electron microscopy) studies are used to examine vesicle release.
• Omega figures ($\Omega$) are observations from the fusion of vesicle and membrane during exocytosis.
• Freeze fracture techniques aid in observing membrane structures.

Physiological View of Exocytosis

• Miniature end-plate potentials (mEPPs) are small, spontaneous depolarizations of the post-synaptic membrane.
• Miniatures represent the fundamental unit of synaptic transmission.
• End-plate potentials (EPPs) are larger depolarizations, summations of mEPPs.
• Exocytosis relates graded potentials (mEPPs) to vesicle release of neurotransmitter.

Jellyfish Aequorin Protein - Bioluminescent Ca++ signal

• Jellyfish aequorin protein is bioluminescent, allowing the measurement of Ca++ influx during pre-synaptic depolarization.
• The influx of Ca++ triggers transmitter release.

Ca++ Channels Regulate NT Release

• The arrival of an action potential depolarizes the presynaptic terminal, opening voltage-gated Ca++ channels.
• Increased Ca++ concentration inside the presynaptic terminal triggers neurotransmitter release via exocytosis.
• Ca++ plays a significant role in the regulated release of neurotransmitters.

Exocytosis and Endocytosis

• Capacitance measurements monitor membrane area changes during exocytosis and endocytosis.
• Exocytosis increases membrane capacitance, and endocytosis decreases it.
• Exocytosis can occur in two forms: classical and "kiss-and-run".

SNARE Complex

• SNARE complex proteins regulate synaptic vesicle fusion with the presynaptic membrane.
• These proteins comprise the membrane fusion process.

Toxins Affecting Ca Mechanism

• Botulinum toxin and tetanus toxin affect neurotransmitter release through targeting SNARE proteins.

Neurotransmitters: 1. Acetylcholine

• Acetylcholine (ACh) is synthesized by Choline acetyltransferase (ChaT).
• Acetylcholinesterase (AChE) breaks down ACh in the synaptic cleft.
• ACh uptake and reuse are critical in synaptic function.

Glutamate - Major CNS Excitatory Transmitter

• Glutamate activates AMPA and NMDA receptors, leading to postsynaptic excitatory potentials (EPSPs).

Amino Acid Transmitters

• GABA is a major inhibitory neurotransmitter in the CNS.
• Glycine is another inhibitory neurotransmitter in the CNS.
• GABA and glycine open chloride channels, which lead to inhibitory postsynaptic potentials (IPSPs).

Neuropeptides

• Neuropeptides act as both neurotransmitters and neuromodulators.
• They are involved in slow, sustained responses compared to classical neurotransmitters.
• These peptides are synthesized in the cell body and transported to terminals.

Biogenic Amines

• Biogenic amines like dopamine, norepinephrine, serotonin, and histamine are synthesized from aromatic amino acids.
• These neurotransmitters play diverse roles in the nervous system.

Uptake and Synthesis of NTs

• Neurotransmitter removal from the synapse is crucial.
• Glial cells and neurons participate in reuptake processes.
• Enzymes like monoamine oxidase (MAO) break down neurotransmitters, affecting neurotransmitter function in neurons.

Enzymatic Breakdown of Amines

• Monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) are enzymes that break down amines like dopamine and norepinephrine.

Pharmacological Intervention at Aminerrgic Synapses

• Various drugs target processes like dopamine synthesis, dopamine reuptake, or adrenergic receptor activation for therapeutic purposes.
• Specific neurotransmitter systems are targeted via drugs for various conditions.

Myasthenia Gravis

• Myasthenia gravis is an autoimmune disorder affecting neuromuscular transmission.
• Myasthenia gravis results in the degeneration of acetylcholine (ACh) receptors.

Ligand-Gated Ionotropic Receptors

• Ionotropic receptors are receptors linked to ligand-gated ion channels.
• Transmembrane depolarization and hyperpolarization are induced by excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs).
• Ligand-gated ion channels mediate fast neurotransmission.