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Printable Handouts
Navigable Slide Index
- Introduction
- Outline
- What are channelopathies
- Conceptual framework for thinking about channelopathies
- Only ~1% of the human genome consists of protein-coding DNA
- Functional subtypes of DNA that are potential sites of sequence modification in genetic disease
- What is a gene?
- What is a mutation?
- Alleles are classified based on their frequency within the population
- Central dogma of molecular biology - extended
- Relationship between genotype and phenotype
- Example 1 – human β-globin gene
- Example 2 – P/Q Ca2+ channel gene (CACNA1A)
- Example 3 – P/Q Ca2+ channel gene (CACNA1A)
- Example 4 – P/Q Ca2+ channel gene (CACNA1A)
- Factors affecting the relationship between genotype and phenotype
- Classification of ion channelopathies
- Classification based on clinical disorder
- Classification based on channel structure and function
- Characterization of permeation and gating
- Classification based on permeation and gating
- Voltage-gated Ca2+ channels
- Ca2+ channel subunit structure/transmembrane topology
- Channelopathies mutations in voltage-gated Ca2+ α1 subunits
- Examples of human Ca2+ channelopathies
- CACNA1S
- CACNA1S channelopathies
- CACNA1S mutations that have been linked to: hypokalemic periodic paralysis (HypoPP)
- HypoPP mutation R1239H and physiological membrane potentials
- CACNA1A
- CACNA1A (P/A-type Ca2+) channelopathies
- Episodic ataxia type 2 (EA2)
- Example – human EA2 mutation F1491S
- Familial hemiplegic migraine type 1 (FHM1)
- Human FHM1 mutation R192Q in mice
- Spinocerebellar ataxia type 6 (SCA6)
- Spinocerebellar ataxia type 6 (SCA6) II
- P/Q Ca2+ channel mutations: cellular level – intrinsic excitability
- P/Q Ca2+ channel mutations: small circuit level – synaptic transmission
- Research on Ca2+ channelopathies
- Summary
- Readings
Topics Covered
- Channelopathies
- Voltage-gated Ca2+ channels
- Human β-globin gene
- P/Q channels
- CACNA1A
- CACNA1S
Talk Citation
Friel, D. (2022, January 31). Calcium channelopathies [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 5, 2024, from https://doi.org/10.69645/WVEL9801.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. David Friel has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Biochemistry
Transcript
Please wait while the transcript is being prepared...
0:00
This is a presentation on "Calcium Channelopathies".
My name is David Friel from
the Department of Neurosciences at Case Western Reserve University.
My research focuses on calcium and electrical signaling
in excitable cells and the impact of
calcium channel mutations on
electrophysiological properties of cells involved in cerebellar motor control.
0:20
In this presentation, we'll start by defining what we mean by channelopathies and present
a conceptual framework for discussing them that
is based on the central dogma of molecular biology.
We will then discuss classification of channelopathies based on
clinical syndrome and based on the ion channels that are defective.
This will be followed by a discussion of voltage-gated calcium channel,
which will be the focus of our discussion of calcium channelopathies.
We will then present several examples of
human calcium channelopathies that span the range of
phenotypic complexity and illustrate
general concepts that are relevant to other channelopathies.
This will be followed by a summary of the main points in the presentation.
1:01
Let's start by defining what we mean by channelopathies.
Channelopathies are diseases that result from defects in ion channel function.
Channelopathies can be classified based on whether they are inherited or acquired.
But for our purposes,
it will be more useful to classify them based on whether they
result from genetic versus non genetic causes.
Genetic causes involve modification of genes that encode channel proteins,
which either occur in germ cells and can be passed on to
offspring or in somatic cells as a result of de novo mutations.
Non-genetic causes include actions of drugs or
toxins or autoimmune attack of ion channels.
While the focus of this presentation will be on
channelopathies that result from modification of channel genes,
two examples of channel disorders that result from non-genetic causes
are cardiac arrhythmias such as long QT syndrome,
which can result as a side effect of
some pharmacological agents used to treat other disorders that alter
the activity of ion channels important for
normal cardiac function. And Lambert-Eaton myasthenic syndrome,
an autoimmune disease characterized by lots of
presynaptic calcium channels at the neuromuscular junction leading to muscle weakness.