Electrical Synapses /Gap Junctions Flashcards
What is a Gap junction?
cell-cell communication
-an array of intercellular channels for direct cell-cell communication
- the two cells get a taste of each others intercellular environments
- cell communicates directly with one another without going into its environment using gap junctions.
What are gap junctions composed of?
connexins
( connexon are the proteins that make connexins )
gap junctions are made up of many of these connexon channels - 12 connexon proteins
co-expression of connexins can lead to complex assemblies of subunits
the connexon genes can be organised in a variety of different ways ( e.g. human has 21 connexon genes )
how are intercellular channels at gap junctions placed?
- they are densely packed together
What are gap junctions said to be ?
- Ubiquitous !!!! ( found everywhere !)
- they are present in all cells in the body !
however
the distribution of connexons is unknown
Give examples when gap junctions mediate bidirectional signalling ?
gap junctions mediate bidirectional signalling:
- between oocytes and granulosa cells. ( two different connexins seen - one - for the nerves oocyte;the second forms the network of granulosa cells )
- between epithelical cells and the gut
What is the permeability of gap junctions like?
Gap junction Channels are peamable to:
- inorganic ions (e.g. K+,Na+,Cl-, HCO3)
- small organic ( signalling ) molecules ( e.g. cAMP , IP3)
- dyes
- metabolites (e.g.Glucose )
What is connexin - Mediated ‘bystander effect ‘ in tumorigenesis ?
bystander effect:The radiation-induced bystander effect (bystander effect) is the phenomenon in which unirradiated cells exhibit irradiated effects as a result of signals received from nearby irradiated cells
( refer to p5 of notes for important example)
what happpens if conexon genes mutate?
- they can be inherited and become diseases
what did Golgi and Cajal beleive about electrical synapses?
- Golgi believed- neurons communicate through gap junctions ( a direct communication between neurons )
- Cajal believed - neurons communicate through chemical neurotransmitters
Is synaptic transmission mediated by chemicals?
- evidence- hyperpolarizing inhibition ( when there is a hyperpolarisation cells release an inhibitory synapse )
What are electrical synapses ?
- they are Gap junctions between Neurons
- composed of connexin 36 (cx36)
- there are 20 different connexin genes - half are expressed in the brain - most connexins in the brain are expressed by Glia - and the most important protein in eleectrical synapses is cx36!!!
Two types of synapses?
- Chemical
- electrical
What is an electrical synapse?
assaying function:
- there are less of them , and they may not be very reliable
- less information is derived from them.
- it is a ‘terminal procedure’ once applied - cannot be reused
Dual cell electrophysiology:
– electrodes were used to record the membrane potential between cells and gap junctions
Dye coupling
method;
- a dye was injected
- when the network of cells contains a gap junction the dye can go through
electrical synaptic transmission:
- electrical synapses can pass Subthreshold current - which does not allow action potentials to occur !
- action potentials result in strongly attenutated post synaptic responses called spikelets
- electrical synapses are bidirectional
- show no preference for depolarizing or hyperpolarizing responses
- electrical synapses are sign preserving
Hyperpolarization in one cell will evoke a change in another cell.
what is a coupling coefficient?
- the ratio between the voltage change observed in the non- injected neurons
what are the differences between electrical and chemical synapses?
electrical vs chemical
- structural differences, close opposition of membranes for electrical
- electrical synapses activate faster than chemical ones : synaptic delay
- electrical transmission is ionic current whereas chemical requires neurotransmitter release and binding
- electrical synapse are almost always bidirectional ; chemical synapses are NOT !
- chemical synapses are de/hyperpolarizing ; electrical synapses show no such specificity
- electrical synapses are sign preserving , chemical are not !
- electrical synapses are reliable , reliability at chemical synapses varies.
- chemical synapses are metabolically expensive , ( 47% of energy at synapses linked to action potentials ! - 34% of biochemical processes involved in synaptic transmission)
- both show modifiable strengths ( e.g. LTP and LTD at chemical synapses )
- both generate chemical or pass electrical subthreshold signals
- electrical has a delay?? or is it chemcial ? !!!
( refer to page 11 of notes !! for diagram !)
What are the tests for electrical and chemical synapses?
Electrical : -
- loop for gap junction
- fast transmission without synaptic delay dual recording should show direct coupling between neurons
- dye coupling !
Chemical:
- look at morphology
- look at proteins associated with vesicle docking and release
- look for synaptic delay
- low Ca 2+ / high Mg2+ should decrease transmission
- receptor antagonists should block transmission
- synaptic reversal potential
What are some network properties ?
- bidirectionality ( from one cell to the next and vice versa)
- shorter synaptic delay ( instantaneous response )
- sign preservation
- mediates both hyperpolarization and depolarizing responses
- facilitates synchrony ( both , sub and supra - threshold ) and promotes action potentials
- coordinates activity in cell - to - cell fashion of a large population
N.B. electrical synapses can promote action potentials.
electrical synapses create a network of… ( finish sentence)
- electrical synapses create a network of synchronously coactive neurons !
- but all show depolarization and hyperpolarization
- may not all fire action potential !
- they all behave as one pool and are all coordinated !
what can create multiple groups of coupled interneurons ?
- Cx36 !
in many brain regions cx36 expression is restricted to interneurons
- interneurons comprise many different subtypes
- cx36 typically couples only similar interneuron subtypes
- thus electrical synapses create electrically coupled homocellular assemblies
(neurons are not identical ! they form chemical synapses randomly !!)
- specificity in Cx36 assembly creates multiple networks of synchronously coactive neurons !
- synchrony generates brain rythms ? - perhaps cx36 is vital ?
What is the importance of electrical synapses?
- what happens if electrical synapses are eliminated from the brain-
- the example of the CX36 knockout mouse !
- results:
- they are viiable ,
- have retinal defects( total night blindness)
- impairment in complex motor learning tasks
- impairment of fine motor control
- deficits in circadian behaviour !
(N.B. mouse has 20 connexon genes - we have 21 ! - and in humans if the vast majority are mutated this can cause disease..)
Why do the mice (Cx36 knockout ) in the experiment have motor impairments ?
- electrical synapses are important in neural circuits related to the cerebellum
What is the strongest synapse in the brain?
- when the purkinje cell receives the very strong signal from the inferior olive
What could be the cause of a motor impairment?
- neurons in the olive generate subthreshold rhythms , which occasionally trigger action potentials , which send signals to the cerebellum.
- the membraned rhythms in neurons of the olive are synchronised
- synchrony requires electrical synapses - and therefore since we know that electrical synpaases requier Cx36 !!!
- the Cx36 is knocked out of these mice -olivary neurons can no longer synchronize wheen olivary neurons cannot synchronise , coordination of mmuscle contractions is impaired…
What is the Cx36 role in the retina ?
- why ate the Cx36 knockout mice night blind? - because information from rod photoreceptors must pass through elctrical synapses to reach the outtpur - ganglion cells. - and since rod cells dont make contact with ganglion cells the mice are night blind
N,B. rods - dim light photoreceptors
- cones - responsible for visualisation in normal light !
What is a summary of this lecture ?
- in mammals most electrical synapses are comprised of CX36 !!! - b ut other connexins and pannexins may also play a role…
- electrical synapses in the retina are comprised of other connexins as well
- electrical synapses usualy allow ionic current and small organis molecules to pass reliably in both directions
- there are considerable differences between ellectrical and chemical synapses and they together generate the complex electriical activity that encodes brain function
- studies in the Cx36 knockout have clearly demonstratd its importance for a variiety of important functions in the brain retina ( and the pancreas)
