Ion transporters and channels

Question 1

Describe the action of lamotrogene (AED)

Answer 1

• Accesses the voltage-gated sodium channels through fenestration’s (deeply buried binding site)
• The drug is buried deep inside the protein
• Inhibit Voltage-gated sodium channels
• Extend the inactivation period

Question 2

Describe some channelopathies of voltage-gated sodium channels (NAv)

Answer 2

• SCN1A - epilepsy, migraine, autism
• SCN2A - epilepsy, autism, episodic ataxia
• SCN3A - epilepsy
• SCN9A - pain insensitivity and extreme pain disorder

Question 3

Describe some potassium channelopathies

Answer 3

• KCNQ2, KCNQ3, KCNMA1 associated epilepsy syndromes

- KCNA1 associated with episodic ataxia type 1

Question 4

Describe some calcium channelopathies

Answer 4

• CACNA1A episodic ataxia type 2, SCA6 and familial hemiplegic migraine
• CACNA1B myoclonus-dystonia syndrome
• CACNA1F X-linked congenital stationary night blindness
• CACNA1H childhood absence epilepsy

Question 5

Describe how channelopathies work

Answer 5

• mutations can affect channel assembly and or function, pore permeability and inactivation

Question 6

Describe the channelopathy for SCA6 (spinocerebellar ataxia type 6)

Answer 6

• Nucleotide repeat of 16-18 glut amines in a row which inactivates the calcium channel

Question 7

What is dominant-negative channelopathy

Answer 7

Where you may have only one single mutation that is enough to poison the whole complex and prevent it from functioning

Question 8

Transient receptor potential channels

Answer 8

• non-selective cation channels

- can be gated by temperature, ligands (nitric oxide) or chemical stress