Non canonical functions of voltage-gated sodium chanenels

Question 1

Timing of life events
DNA replication and cell division

Answer 1

1 day

Question 2

Timing of life events
Gene transcription / protein syntesis

Answer 2

1 hour

Question 3

Timing of life events
Hormone regulation

Answer 3

1 min

Question 4

Timing of life events
Enzymatic activity

Answer 4

0.1 - 1 sec

Question 5

Timing of life events
Electrical signals
(vision, hearing, nerve conduction, muscle conduction)

Answer 5

1 millisec

Question 6

Moving ions make electronical signals

Answer 6

Ascendent rapid phase : Na+ enters in the celle -> inside positive
Descending phase : K+ leaves the cell -> returns to negative resting potential

Question 7

Mesurement of electrical signals

Answer 7

we use patch clamp technique

Question 8

Conformational states of sodium channels

Answer 8

Close state
Activates/open state
Inactivated state : the ions cannot pass because of a blocking protein
to be open again we have to wait = “phase de latence”

Question 9

Perfect model to study sodium channels

Answer 9

Squid

Question 10

Toxins to paralyze prey

Answer 10

Toxins target sodium channels to paralyze prey :
opiates can supress the possibility to inactivate the channels by blocking the blocking protein
Toxins in different animals like spiders, scorpions and snakes

Question 11

To paralysis a prey

Answer 11

Alpha scorpion toxin slows down the mecanism of inactivation, the fibres and the nerves are blocked => paralysis

Question 12

TTX

Answer 12

Specific way of killing and cooking it otherwise he will intoxicate you
Toxin called Tetrodotoxin (TTX)
produced by a marine bacterium
It blocks activity of Na+ channels

Question 13

Local anesthesics

Answer 13

preventing the pain by blocking the activity of Na+ channels
Other blocking drugs are used in treatments of epilepsy, cardiac arythmia ans chronic pain.

Question 14

Discovery of sodium channel protein molecule

Answer 14

Work of Pr William CATTERALL
Difficult because more than 20 000 types of proteins molecule in the brain

Question 15

Family of sodium channels

Answer 15

9 members classified depending on the
- TTX-sensibility
- TTX-resistance

Question 16

Caracterised voltage dependent channels

Answer 16

conductance, ion selectivity, pharmacology, voltage-sensitivity

Question 17

Begining of the story cancer/Na+ channels

Answer 17

If there is a membrane you can patch it !

Question 18

Cancer cells

Answer 18

When you block the activity of the Na+ channells by using TTX, you decrease the number of cells that are invading
Inhibition des protéines Nav 1.5 diinue l’invasion des cellules cancéreuses

Question 19

Breast cancer over expression of ARN transcript of the proteins of Nav 1.5

Answer 19

associated with a poor prognostic
Same for colon cancer

Question 20

Cervical cancer

Answer 20

Nav 1.6
use specific toxin (TTX) -> inhibit the invasive capacity by about 20%

Question 21

pH

Answer 21

pH increases after blocking of the channels

Question 22

Ranolazine breast cancer

Answer 22

used to treat cardiomyopathy because it blocks Nav1.5
could be very useful to fight metastasis in organisms

Question 23

Phenotoin

Answer 23

inhibits breast tumor growth and metastasis

Question 24

Ronolazine prostate cancer

Answer 24

Anti-metastatic effect of Ronolazine using an in vivo rat model of prostate cancer
- reduces tumor volume
- reduces the number of metastasis

Question 25

Conclusion

Answer 25

The targeting of these txo preteins (Nav and NHE1) is an opportunity to fight and decrease metastasis.