Channelopathies Flashcards
Give some causes of channelopathies.
radiation, infection, chemicals and toxins, germline (error in DNA replication), somatic (problem in developement) and scientists use it as an experimental tool.
Explain what a point mutation is.
1 base change. It is most likely to cause an AA change if in the 1st base of a codon.
Explain what a nonsense mutation is.
Base change that causes a STOP codon.
Explain what a frame shift mutation is.
Insertion of a base.
What is an autosomal dominant disease?
Disease is expressed in the heterozygote.
What is an autosomal recessive disease?
Disease is expressed in the homozygote - heterozygote is a carrier.
What is a dominant negative disease?
One mutant protein affect the funtioning of the whole protein.
What is haploinsufficeny?
Both genes is required for full functioning.
Define mutation and polymorphism.
Mutation only occurs in less than 1 % of the population.
Polymorphism occurs in more than 1% of the population.
Describe the channelopathy associated with the disease hyperekplexia.
Muscle spasm in response to unexpected stimuli, becomes rigid and falls over. Increased muscle tone as an infant (hypertonia).
Autosomal dominant disease. 5q32, same place as gene for glycine receptor.
R271Q (arginine for glutamate).
Channel is still there - ligand binding is affected. Decrease glycinergic inhibition in the spinal cord.
Leads to exaggerated reflexes, exaggerated startle response and hypertonia.
Describe the channelopathy associated with Generalised Epilepsy with Febrile Seizures (GEFS).
Convulsions, fever, 3% children younger than 6. Some go on to develop generalised epilepsy later in life.
Autosomal dominant. 19q31.1 - same place as the SNC1B (sodium channel B1 subunit).
C121W - cysteine for tryptophan.
Beta subunit isn’t pore forming of voltage sensing but it does associate with the large alpha subunit. The beta subunit alters the kinetics of the channel. Makes the sodium channel less likely to shut.
This leads to…
…slower inactivation
…more depolarised Vm = hyperexcitability
…persistant slow inwards Na current
…BUT, most symptoms resolve and it is temperature dependant?
Describe the channelopathy associated with Benign Familial Neonate Convulsion (BFNC).
Recurrent seizures early in life. 3 days to 3 months old.
Haploinsufficiency - 20q13.3 - same place as the KCNQ2 channel - potassium channel. 300 AA deletion - non functioning K+ channel = hyperexcitablilty,
Notmall KCNQ2 and KCNQ3 subunits make channels in PNS/CNS.
The M currents control reptitive firing in neurones - neurone has a tonic firing rate to a sustained stimuli - very excitable!!
