Synapses and Synaptic Transmission

Electrophysiology II

Synapse

Electrical Synapse• Gap junctions

Chemical Synapse• Synaptic cleft

Stages of Chemical Synaptic Transmission

• Synthesis of NTs• Release of NTs• Activation (or inhibition) of post-synaptic

receptors– i.e. NMJ

• Inactivation of NTs

Synthesis of NTs• If small molecule non-peptides then pre-

synaptic nerve terminals• If neuropeptides then pre-synaptic nerve cell

body• Stored in vesicles – Have receptors that, when activated, will trigger

release of stored NTs

Release of NTsAction potential (AP) -> membrane depolarization -> Voltage-gated Ca++ channels activated -> influx of Ca++ ions -> Ca++ ions bind to synaptotagmin -> vesicular mobilization -> synaptobrevin (from vesicle) binds to plasma membrane binding proteins (i.e. SNAP-25, and syntaxin-1) -> fusion of plasma membrane and vesicle (fusion pore) -> exocytosis of NTs to synaptic cleft

Autoregulation of NTs release

Vesicles• Small vesicles -> small NTs (non-peptide)• Large vesicles -> large NTs (neuropeptide)• ↓number of AP -> release of small NTs• ↑number of AP -> release of both small and

large NTs

Activation of post-synaptic receptors• Ionotropic– Involves ion channels– Fast synaptic potentials

• Metabotropic– Involves G-protein coupled receptors– Also involves ion channels indirectly– Slow synaptic potentials

Neurotransmitters• Excitatory– Trigger excitatory post-synaptic potentials (EPSP)– Making the cell more positive

• Influx of positive ions (e.g. Na+)• Efflux of negative ions (e.g. Cl-)• Prevention of influx of negative ions• Prevention of efflux of positive ions

– Glutamate (most common excitatory neurotransmitter)

Neurotransmitters• Inhibitory– Trigger inhibitory post-synaptic potentials (IPSP)– Making the cell more negative

• Efflux of positive ions (e.g. K+)• Influx of negative ions (e.g. Cl-)• Prevention of efflux of negative ions• Prevention of influx of positive ions

– GABA (spinal cord) and glycine (whole nervous system) are inhibitory NTs

Modulation of release of NTs• Three mechanisms– Increased Cl- influx– Increased K+ efflux– Inhibition of Ca++ influx

• Remember GABA (inhibitory NTs)– GABAA (ionotropic)

– GABAB (metabotropic)

MEMORIZE!!

Termination of NT action• Rapid on and off responses• To prevent down-regulation of receptors• Mechanisms– Diffusion– Degradation– Re-uptake– Uptake by non-neuron cells (glial cells)

ACh, EPP, and NMJ• Neuromuscular junction (NMJ)– Post-synaptic– Activated by Acetylcholine (ACh) producing end-

plate potentials (EPP)

NMJ activation(?) -> ACh release -> binding to ACh receptors -> influx of Na+ ions(to the muscle cell) -> (ACh degraded from synaptic cleft by acetylcholine esterase) -> depolarization (EPP) -> contraction*

*muscle physiology module

Denervation of skeletal muscle• Fibrillation potentials– Replacement of fetal Na+ channels (more

excitable)– If re-innervated, Na+ channels are reverted to the

adult type