LECTURE 3 - synapses; ionotropic receptors Flashcards
What are the two main types of receptors?
- Direct: ligand-gated ion channels (ionotropic)
2. Indirect: G-protein coupled (metabotropic)
What are the two electrical effects of synaptic transmission?
- Excitatory = depolarisation due to Na+ influx USUALLY
2. Inhibitory = hyperpolarisation due to Cl- influx
What is an EPSP and how is it generated?
EPSP = excitatory postsynaptic potential
- temporary depolarisation of the postsynaptic membrane caused by the flow of +ve ions as a result of the opening of V-gated channels
Describe an example of excitatory synaptic transmission in the CNS
1a/ motor neurone synapse Neurotransmitter = glutamate receptors: 3 ionotropic - 1x NMDA - 2x non-NMDA (AMPA, kainate) 1 metabotropic
Describe the synaptic connections in the stretch reflex
- muscle spindle gets stretched, gets activated, 1a afferent sensory neurone sends AP
- 1a sensory neurone –> extensor motor neurone = EPSP
- interneurone –> flexor motor neurone = IPSP
- combined activation = contraction of extensor muscle and relaxation of flexor muscle
What is an NMDA receptor?
- 1 of 3 types of ionic glutamate receptors (others are AMPA and kainate receptors)
- activated by glutamate to open cation channel, Na has large driving force, K driving force is less, membrane potential close to Ek
- permeable to Ca2+: channel opens, Ca enters
- blocked by EXTRACELLULAR Mg and APV
How is NMDA receptor channel CURRENT recorded?
- electrode pushed against surface (not piercing), patch of membrane isolated so activity of only 1 channel is measured
- glutamate is in micropipette to activate channel opening
- can be done in either presence or absence of Mg
Explain glutamate receptor activity in the ABSENCE of extracellular Mg2+
NEGATIVE Vm:
- channel opens downwards (-ve current = inward movement) due to excess of Na+ entry
POSITIVE Vm:
- channel opens upwards (+ve current = outward movement) due to excess K+ exit
- at +ve voltages, driving force on K is larger than Na therefore K moves out
At 0mV:
- no visible activity (current = 0)
- this is the current reversal potential (Erev)
- due to channel being permeable to both Na+ and K+
- Erev ~ halfway between ENa and Ek i.e. Na(in) = K(out)
Explain glutamate receptor activity in the PRESENCE of extracellular Mg2+
- produced voltage-dependent channel block
- channel opening unaffected at +60mV as Mg2+ repelled by +ve Vm
- at increasingly negative Vm, channel openings are briefer
- Mg2+ is attracted into channel at -ve Vm
How do you measure a glutamate excitatory postsynaptic current (EPSC)?
Objective: to measure current flowing through all of the glutamate receptor channels during synaptic activation
Procedure:
- voltage clamp of POSTsynaptic cell
- stimulate PREsynaptic axon to generate AP
- -> glutamate release
- -> opening of receptor channels
- repeat stimulation but use APV to block NMDA channels
What would be observed when measuring a glutamate EPSC?
- at -60mV EPSC is inward (mostly Na+ influx) and brief
- APV has no effect as Mg2+ is blocking NMDA channels
What is the physiological important of NMDA receptors?
- only non-NMDA channels contribute to EPSC following single stimulation
- repeated synaptic activation = summation of EPSPs (ie increased depolarisation)
- Mg2+ block of NMDA channels partly relieved
- NMDA can now contribute to EPSP
- Plus Ca2+ enters the cell
What are the consequences of Ca2+ entering a cell following an EPSP?
- enzyme activation
- release of retrograde factor
- increased glutamate release (i.e. enhanced synaptic function) - synaptic plasticity
What is an IPSP?
Inhibitory postsynaptic potential: hyperpolarisation
What are the inhibitory synapses neurotransmitters and ionotropic receptors?
Neurotransmitters: glycine (spinal cord) and GABA (brain)
Receptors:
Glycine and GABA(A) receptors - chloride channels
