Lecture 12

Question 1

What are Gap Junctions?

Answer 1

Arrays of intercellular channels for direct cell-to-cell communication.

Question 2

What are gap junctiones permeable to?

Answer 2

Gap junctions channels are permeable to inorganic ions (K+, Na+, Cl- and HCO3-), small organic (signalling) molecules (cAMP, IP3), dyes and metabolites.

Question 3

What do gap junctions do?

Answer 3

They coordinate the biochemical and electrical activities of coupled populations in a cell-to-cell fashion.

Question 4

What are gap junctions composed of?

Answer 4

Connexins, which assemble to form a connexon. Other may be formed by pannexins.

Question 5

Describe electrical transmission between MesV neurons:

Answer 5

It is mediated by connexing 36 (Cx36)-containing gap junctions at somato-somatic contacts and only 0.1% of channels are conductive.

Question 6

How many connexin genes are expressed in human genome?

Answer 6

21, half are expressed in te brain, most connexins in the brain are expressed by glia.

Question 7

What are the two types of connexon?

Answer 7

Homomeric or heteromeric

Question 8

What are the two types in addition to homomeric or heteromeric of interecellular channels?

Answer 8

Homotypic and heterotypic.

Question 9

What are two examples that shows the ubiquity of gap junctions?

Answer 9

Gap junctions mediate bidirectional signalling between oocytes and granulosa cells and between epithelial cells and the gut.

Question 10

List three inherited human disorders resulting from connexin mutations:

Answer 10

Cataracts (Cx46 and 50)
Hearing impairment (Cx26, 30 and 31)
Charcot-Marie-Tooth type X - CMTX (Cx32)

Question 11

What doctrine did Cajal supported?

Answer 11

The neuron doctrine

Question 12

What theory did Golgi supported?

Answer 12

The reticular theory.

Question 13

When were electrical synapses demonstrated and by who?

Answer 13

In 1959 by Fursham and Potter.

Question 14

When and who discovered gap junctions?

Answer 14

In 1967 by Revel and Karnovsky.

Question 15

What are electrical synapses structurally speaking?

Answer 15

Neuronal gap junctions composed of connexin 36 (Cx36).

Question 16

Describe dye coupling as an assaying function for electrical synapses:

Answer 16

Easier but not reliable, may show some specificity for neuronal connexin type. It gives less information about electrical synapse, cell and network and is a terminal procedure, once applied cannot be reused.

Question 17

What is coupling coefficient?

Answer 17

The ratio between the voltage change observed in the non-injected and the injected neuron.

Question 18

List some of the properties of electrical transmission:

Answer 18

• Electrical synapse can pass subthreshold current.
• Are bidirectional
• APs result in strongly attenuated postsynaptic responses called spikelets
• Show no preference for depolarizing or hyperpolarizing responses
• Sign preserving (only excitatory).

Question 19

What are the two main difference between electrical and chemical synapses?

Answer 19

Structural differences: close opposition of membranes for electrical
Electrical synapses activate faster than chemical ones.

Question 20

How is metabolic expenditure different between electrical and chemical synapses?

Answer 20

Chemical synapses are metabolically expensive, 47% of the energy at synapses is linked to AP, 34% of biochemical processes is involved in synaptic transmission.

Question 21

At the level of the network, what are two important characteristics of gap junctions?

Answer 21

1) Facilitates synchrony (both sub and suprathreshold) and promotes action potentials
3) Coordinates activity in cell-to-cell fashion of a large population.

Question 22

Describe how Cx36 Ccan create multiple groups of coupled interneurons:

Answer 22

In many brain regions Cx36 expression is restricted to interneurons. Cx36 typically couples only similar interneuron subtypes hence creating electrically coupled homocellular assemblies.

Question 23

What happens if you eliminate electrical synapses from the brain?

Answer 23

-Cx36 knockout mouse are viable
-Have retinal deficits (total night blindness)
Impairment of motor control
-EEG abnormalities
Impairment in more complex motor learning tasks, object memory, and habituation
-Deficits in circadian behavior.

Question 24

Why do Cx36 knockout mice have problems with motor control?

Answer 24

Electrical synapses are important in neural circuits related to the cerebellum (in the inferior olive). Neurons in the olive generate subthreshold rhythms which occasionally trigger action potentials which send signals to the cerebellum.

Question 25

Why is membrane rhytms in the olive impaired in Cx36 knockout mice?

Answer 25

The membrane rhythms in neurons in the olives are synchronized; synchrony requires electrical synapses, which in turn requires Cx36.

Question 26

What happens when olivary neurons cannot synchronize anymore (like in Cx36 KO mice)?

Answer 26

Coordination of muscle contraction is impaired and ataxia occurs.

Question 27

What is the role of Cx36 in retina?

Answer 27

Information from rod photoreceptors must pass through electrical synapses to reach output (ganglion) cells.