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Biomembranes > Electrical Synapses /Gap Junctions > Flashcards

Electrical Synapses /Gap Junctions Flashcards

1
Q

What is a Gap junction?

A

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.
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2
Q

What are gap junctions composed of?

A

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 )

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3
Q

how are intercellular channels at gap junctions placed?

A
  • they are densely packed together
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4
Q

What are gap junctions said to be ?

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

however
the distribution of connexons is unknown

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5
Q

Give examples when gap junctions mediate bidirectional signalling ?

A

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
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6
Q

What is the permeability of gap junctions like?

A

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 )
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7
Q

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

A

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)

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8
Q

what happpens if conexon genes mutate?

A
  • they can be inherited and become diseases
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9
Q

what did Golgi and Cajal beleive about electrical synapses?

A
  • Golgi believed- neurons communicate through gap junctions ( a direct communication between neurons )
  • Cajal believed - neurons communicate through chemical neurotransmitters
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10
Q

Is synaptic transmission mediated by chemicals?

A
  • evidence- hyperpolarizing inhibition ( when there is a hyperpolarisation cells release an inhibitory synapse )
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11
Q

What are electrical synapses ?

A
  • 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!!!
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12
Q

Two types of synapses?

A
  • Chemical

- electrical

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13
Q

What is an electrical synapse?

A

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.

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14
Q

what is a coupling coefficient?

A
  • the ratio between the voltage change observed in the non- injected neurons
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15
Q

what are the differences between electrical and chemical synapses?

A

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 !)

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16
Q

What are the tests for electrical and chemical synapses?

A

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
17
Q

What are some network properties ?

A
  • 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.

18
Q

electrical synapses create a network of… ( finish sentence)

A
  • 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 !
19
Q

what can create multiple groups of coupled interneurons ?

A
  • 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 ?
20
Q

What is the importance of electrical synapses?

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

A
  • 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..)

21
Q

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

A
  • electrical synapses are important in neural circuits related to the cerebellum
22
Q

What is the strongest synapse in the brain?

A
  • when the purkinje cell receives the very strong signal from the inferior olive
23
Q

What could be the cause of a motor impairment?

A
  • 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…
24
Q

What is the Cx36 role in the retina ?

A
  • 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 !

25
Q

What is a summary of this lecture ?

A
  • 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)

Biomembranes (15 decks)

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