Electrical Synapses /Gap Junctions

Question 1

What is a Gap junction?

Answer 1

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.

Question 2

What are gap junctions composed of?

Answer 2

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 )

Question 3

how are intercellular channels at gap junctions placed?

Answer 3

• they are densely packed together

Question 4

What are gap junctions said to be ?

Answer 4

• Ubiquitous !!!! ( found everywhere !)
• they are present in all cells in the body !

however
the distribution of connexons is unknown

Question 5

Give examples when gap junctions mediate bidirectional signalling ?

Answer 5

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

Question 6

What is the permeability of gap junctions like?

Answer 6

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 )

Question 7

What is connexin - Mediated ‘bystander effect ‘ in tumorigenesis ?

Answer 7

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)

Question 8

what happpens if conexon genes mutate?

Answer 8

• they can be inherited and become diseases

Question 9

what did Golgi and Cajal beleive about electrical synapses?

Answer 9

• Golgi believed- neurons communicate through gap junctions ( a direct communication between neurons )
• Cajal believed - neurons communicate through chemical neurotransmitters

Question 10

Is synaptic transmission mediated by chemicals?

Answer 10

• evidence- hyperpolarizing inhibition ( when there is a hyperpolarisation cells release an inhibitory synapse )

Question 11

What are electrical synapses ?

Answer 11

• 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!!!

Question 12

Two types of synapses?

Answer 12

• Chemical

- electrical

Question 13

What is an electrical synapse?

Answer 13

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.

Question 14

what is a coupling coefficient?

Answer 14

• the ratio between the voltage change observed in the non- injected neurons

Question 15

what are the differences between electrical and chemical synapses?

Answer 15

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 !)

Question 16

What are the tests for electrical and chemical synapses?

Answer 16

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

Question 17

What are some network properties ?

Answer 17

• 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.

Question 18

electrical synapses create a network of… ( finish sentence)

Answer 18

• 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 !

Question 19

what can create multiple groups of coupled interneurons ?

Answer 19

• 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 ?

Question 20

What is the importance of electrical synapses?

- what happens if electrical synapses are eliminated from the brain-

Answer 20

• 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..)

Question 21

Why do the mice (Cx36 knockout ) in the experiment have motor impairments ?

Answer 21

• electrical synapses are important in neural circuits related to the cerebellum

Question 22

What is the strongest synapse in the brain?

Answer 22

• when the purkinje cell receives the very strong signal from the inferior olive

Question 23

What could be the cause of a motor impairment?

Answer 23

• 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…

Question 24

What is the Cx36 role in the retina ?

Answer 24

• 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 !

Question 25

What is a summary of this lecture ?

Answer 25

- 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)