channelopathies Flashcards
What are neurological channelopathies?
Disorders of ion channels
What are the two main types of channelopathies based on origin?
- Inherited (e.g. mutations)
- Acquired (e.g. toxins; trauma; autoimmune)
What is a common feature of channelopathies?
Discrete attacks (symptoms that come and go, short period of time and then comes back)
What are some brain manifestations of channelopathies?
- Epilepsy (seizures)
- Migraine
What are the manifestations of channelopathies in the cerebellum, spinal cord, and brainstem?
- Movement disorders (e.g. ataxia)
- Loss of motor control
- Excessive startle response
What muscle diseases can be caused by channelopathies?
- Periodic paralysis
- Myotonia
What mutations can lead to disorders of peripheral nerve and autonomic function?
Mutations in sodium channels
What are the two types of mutations in channelopathies?
- Gain of function (e.g. epilepsy)
- Loss of function (e.g. weakness or numbness)
What factors affect the consequences of mutations in channelopathies?
- Ion channel type and function
- Where and when the channel is expressed
- Biophysical property change (e.g. fast vs slow inactivation)
What is the consequence of channelopathy mutations?
Excessive or decreased/loss of membrane excitability
What causes epilepsy in the context of channelopathies?
Hyperexcitability due to spontaneous firing of large group of neurons
Which types of ion channels are often defective in epilepsy?
- Voltage-gated K+ channels
- Na+ channels
- Ca2+ channels
- Ligand-gated ion channels (e.g. GABA-A)
How does the malfunction of GABA-A receptors affect the brain?
It leads to hyperexcitability due to decreased activity of inhibitory neurons
What mutation causes inherited erythromelalgia (IEM)?
Gain of function mutation in the SCN9A gene
What is the role of the Nav1.7 sodium channel in inherited erythromelalgia?
Important for pain signaling and shifts voltage gating to more hyperpolarized potentials
What is the result of the mutation in the Nav1.7 sodium channel?
Too much nerve activity and increased action potential firing
What are the symptoms of inherited erythromelalgia?
Intense burning pain
What causes episodic ataxia type 1 (EA1)?
Mutations in the KCNA1 gene encoding for the voltage-gated Kv1.1 potassium channel
What triggers episodes of poor motor coordination in EA1?
Stress or exercise
How does the mutation in the KCNA1 gene affect neuron activity?
The channel opens too late and closes too quickly
What is impaired in action potentials due to mutations in EA1?
Repolarization
What is the result of longer action potentials in EA1?
Uncontrolled nerve firing and motor coordination problems
