Excitatory and Inhibitory Neurotransmission in the CNS Flashcards
Effect of depolarisation in neurons
leads to transmitter release
Effect of entry of + ions (Ca, K, Na) or exit of - ions (Cl)
results in a positive charge (depolarisation/excitation)
Effect of exit of + ions or entry of - ions
results in negative charge (hyperpolarisation or inhibition)
Action of Na channel agonists
- opens channels
- causes Na flow into cell
- results in excitation
Action of Na channel antagonists
- closes channel
- stops Na ion flow
- favours inhibition
- e.g. local anaesthetics
Action of K channel agonist
- opens K channel
- causes K flow out of cell
- makes cell more negative
- inhibitory
Action of K channel antagonist
- closes K channel
- retains K in cell
- favours positive rmp
- excitatory
Describe the events that take place at the synapse
- AP depolarises axon terminal
- depolarisation opens voltage-gated Ca channels and Ca enters cell
- Ca entry triggers exocytosis of vesicles
- NT diffuses across synaptic cleft and binds with receptors on post synaptic cell
- NT binding initiates a response in postsynaptic cell
Describe the events that take place at the synapse when NTs are inactivated
- NTs can be returned to axon terminals for reuse or transported into glial cells
- enzymes inactive NTs
- NTs can diffuse out of the synaptic cleft
Role of astrocytes
- buffer potassium
- glutamate released in cleft can be taken up by astrocytes and transported back into neurons
- ensure synaptic cleft is kept clear of NTs
What are the two modes of post-synaptic action of a NT
- directly (ionotropic receptors) or indirectly (metabotropic receptors)
- GABA can act on both receptors
Action of ionotropic receptors
- integral component of molecule
- nAChR channel activation
- membrane depolarisation
- AP excitation
- muscle contraction
Action of metabotropic receptors
- muscarinic ACh receptor activation
- release of alpha-GTP + By from the heterotrimeric G protein
- activation of inward rectifier K+ channel by By
- membrane hyperpolarisation
- decrease in HR
What are the two major families of ligand-gated channels
- GABAA, Glycine and ACh (nicotinic) receptors
- Glutamate receptors
Action of glutamate on glutamate receptors
- may have inhibitory effects via its response at metabotropic glutamate receptors
- ionotropic glutamate receptors directly gate ion channels and may be classified via response to non-endogenous agonists that mimic glutamate
Role of non-NMDA receptors
- bind agonists kainate or AMPA controlling a channel permeable to Na and K
- mediate fast excitatory synaptic transmission in the CNS
Role of NMDA receptors
- controls a channel permeable to Na, Ca, and K
- contributes a slow component to the excitatory synaptic potential
- thought to promote neurotoxicity due to high pereability to Ca
How do metabotropic glutamate receptors exert their effect
by activation of second messenger cascade -> they dont have an integral ion channel
Role of metabotropic glutamate receptors
modulation of neurotransmission e.g. presynaptic inhibition of Ca channels
Role of ionotropic and metabotropic glutamate receptors in retinal pathways
discriminate between on/off retinal pathways
Action of benzodiazepines
positive allosteric modulator of GABA A receptor, enhance Cl entry, decrease rmp, and enhance inhibition in presence of GABA
Action of barbiturates
similar to benzodiazepines and potentiates the effect of GABA at GABA A receptor
Action of baclofen
agonist of the GABA B receptor, enhances K current and increases inhibition
Role of glycine
- inhibitory NT
- acts on glycine ionotropic receptor which gates a Cl channel
- released by interneurons in spinal cord to inhibit antagonist muscles motoneurones
Actions of ionotropic receptors
- gating of ion channels is rapid (ms)
- channels function as on-off switches
Actions of metabotropic receptors
- can act indirectly on a variety of channels
- can close
- usually the slow actions of metabotropic receptors are insufficient to trigger an AP -> rather they have modulatory synaptic actions
- act on neighbouring voltage-gated channels
- actions can occur at presynaptic cell or postsynaptic cell
What are modulatory synaptic actions of metabotropic receptors
- acting on channels in the presynaptic terminal to modulate transmitter release
- modulate transmitter-gated channels to regulate the size of the post synaptic potential
- modulate the resting and voltage-gated ion channels in the neuronal soma to alter e.g. resting Em and AP firing pattern
Cholinergic synaptic transmission in autonomic ganglia
- display both direct and indirect transmitter actions
- fast epsp is due to activation of nicotinic ACh receptors (channels conduct Na and K)
- slow epsp follows activation of muscarinic ACh receptors (ACh closes a K channel (M-type))
Examples of ion channels (ionotropic receptors)
AMPA, NMDA, Kainate, GABA, Glycine, nACh, Seratonin, Purines
Examples of GPCRs (metabotropic receptors)
Glutamate, GABAB, Dopamine, NE Epi, Histamine, Serotonin, Purines, Muscarinic
What region of the brain first receives auditory signals
cochlear nucleus
