Biophysical Properties of Nav1.5
30 Questions
1 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the main function of Nav1.5 in the human heart?

  • Driving the sodium current (INa) (correct)
  • Regulation of heart rate
  • Pumping blood
  • Transmitting electrical signals to the brain

    • Nav1.5 is composed only of α subunits.

    False

    What genetic polymorphism is associated with Nav1.5?

    SCN5A

    The clinical implications of genetic polymorphisms in SCN5A can lead to __________ disorders.

    <p>cardiac</p> Signup and view all the answers

    Match the following publications with their focus area:

    <p>Barc et al. (2022) = Brugada syndrome risk loci O'Reilly et al. (2023) = Familial atrial fibrillation mutation Wisedchaisri et al. (2019) = Voltage-gated sodium channel structure O'Shea et al. (2022) = Cardiac electrophysiology mapping</p> Signup and view all the answers

    Which experimental approach explores cardiac electrophysiology?

    <p>Optical mapping</p> Signup and view all the answers

    Nav1.5 channels are expressed in the brain.

    <p>False</p> Signup and view all the answers

    What mechanism regulates sodium channel activity according to recent studies?

    <p>Genetic polymorphisms</p> Signup and view all the answers

    The pore-forming subunit of the cardiac sodium channel is referred to as __________.

    <p>Nav1.5</p> Signup and view all the answers

    What type of current does Nav1.5 primarily facilitate?

    <p>Sodium current (INa)</p> Signup and view all the answers

    Which of the following major adverse events has been reported with the 'pill-in-pocket' approach?

    <p>Brugada syndrome</p> Signup and view all the answers

    Flecainide was originally developed for the management of ventricular arrhythmia after myocardial infarction.

    <p>True</p> Signup and view all the answers

    What is the common polymorphism in SCN5A associated with increased sensitivity to propafenone?

    <p>R1193Q</p> Signup and view all the answers

    A heterozygous point mutation in SCN5A associated with familial AF is known as _____ (M1875T).

    <p>M1875T</p> Signup and view all the answers

    Match the following drugs with their effects:

    <p>Flecainide = Increases mortality compared with placebo Propafenone = Induces Brugada syndrome ECG pattern Flecainide and Encainide = Management of ventricular arrhythmia Both drugs = Can cause pro-arrhythmia with polymorphisms</p> Signup and view all the answers

    What biophysical property is reduced in MAPRE KO hiPSC-CMs?

    <p>Both A and B</p> Signup and view all the answers

    Polymorphisms in SCN5A do not affect sensitivity to anti-arrhythmic drugs.

    <p>False</p> Signup and view all the answers

    What is a common adverse effect of anti-arrhythmic drugs?

    <p>Pro-arrhythmia</p> Signup and view all the answers

    The biophysical diversity in SCN5A is particularly observed between _____ and right ventricular tissues.

    <p>left ventricular</p> Signup and view all the answers

    Which of the following abnormalities can be explained by understanding biophysical properties of SCN5A?

    <p>QRS duration prolongation</p> Signup and view all the answers

    What condition is associated with gain-of-function mutations in SCN5A?

    <p>Long QT syndrome Type 3</p> Signup and view all the answers

    Brugada syndrome can be unmasked by sodium-channel blockers.

    <p>True</p> Signup and view all the answers

    What gene encodes the Nav1.5 sodium channel?

    <p>SCN5A</p> Signup and view all the answers

    Type 1 Brugada syndrome is caused by _____ mutations in SCN5A.

    <p>loss-of-function</p> Signup and view all the answers

    Match the conditions with their associated genetic mutations:

    <p>Long QT syndrome Type 3 = Gain-of-function mutations in SCN5A Brugada syndrome = Loss-of-function mutations in SCN5A Familial atrial fibrillation = Unknown mutations Sudden infant death syndrome = Genetic predisposition</p> Signup and view all the answers

    Which of the following is NOT a condition associated with genetic polymorphisms of SCN5A?

    <p>Atrial flutter</p> Signup and view all the answers

    There are fewer than 200 mutations associated with Long QT syndrome Type 3.

    <p>False</p> Signup and view all the answers

    What technique uses potentiometric dyes to assess cardiac electrophysiology?

    <p>Optical mapping</p> Signup and view all the answers

    Brugada syndrome has elusive remaining genes, but _____ has been identified recently.

    <p>MAPRE2</p> Signup and view all the answers

    What effect does Type 3 Long QT syndrome have on the action potential duration?

    <p>It prolongs action potential duration.</p> Signup and view all the answers

    Study Notes

    Biophysical Properties of Nav1.5

    • Nav1.5 is a cardiac sodium channel, composed of α and β subunits
    • It's the pore-forming subunit of voltage-gated sodium channels in human myocardium
    • Its function drives sodium current (INa) in the heart
    • The gene SCN5A encodes Nav1.5

    Learning Outcomes

    • Describe the biophysical properties of Nav1.5
    • Describe genetic polymorphisms in SCN5A and their clinical implications
    • Describe suitable experimental techniques for exploring cardiac electrophysiology
    • Barc et al. (2022): Genome-wide association analyses identified new Brugada syndrome risk loci and a novel mechanism of sodium channel regulation in disease
    • S. O. B. et al. (2022): Increased atrial effectiveness of flecainide conferred by altered biophysical properties of sodium channels
    • O’Reilly et al. (2023): Familial atrial fibrillation mutation M1875T-SCN5A increases early sodium current and dampens flecainide effect
    • O’Shea et al. (2022): High resolution optical mapping of cardiac electrophysiology in pre-clinical models
    • Wisedchaisri et al. (2019): Resting-state structure and gating mechanism of a voltage-gated sodium channel

    What is Nav1.5?

    • The cardiac sodium channel is composed of α and β subunits
    • Nav1.5 is the pore-forming subunit of the voltage-gated sodium channel, found in the human myocardium
    • Nav1.5 function drives sodium current (INa) in the human heart
    • The resting state, activated state, and inactivated state are key to the gating mechanism of Nav1.5
    • Depolarization activates the channel
    • Repolarization inactivates the channel

    SCN5A

    • Nav1.5 is encoded by the SCN5A gene
    • Structural components of SCN5A are detailed (TBX5, NF-кB, GATA4, etc. are associated with transcription/translation/assembly and anchoring)
    • Polymorphisms may impact drug action and cardiac conditions.

    Genetic Polymorphisms of SCN5A

    • Long QT syndrome (LQTS)
    • Brugada syndrome (BrS)
    • Early repolarization syndrome
    • Congenital sick sinus syndrome
    • Familial atrial fibrillation
    • Sudden infant death syndrome

    Long QT Syndrome

    • Type 3 LQTS is caused by gain-of-function mutations in SCN5A
    • More than 200 gain-of-function mutations identified
    • Mutations prolong action potential duration (APD), thus increasing QT interval

    Brugada Syndrome

    • BrS type 1 is caused by loss-of-function mutations in SCN5A
    • Characteristic ECG changes can be spontaneous or unmasked by sodium-channel blockers
    • MAPRE2 has been identified as a contributing gene

    Optical Mapping for Cardiac Electrophysiology

    • Fluorescence-based technique using potentiometric dyes in whole tissues or hearts to measure changes in electrophysiology
    • Enables quantification of regional/global changes in electrophysiology in paced specimens

    Major Adverse Events with "Pill-in-Pocket" Approach

    • At therapeutic doses, flecainide and propafenone can cause adverse effects
    • QRS prolongation, Brugada syndrome, and cardiogenic shock are possible complications
    • These complications may be related to SCN5A polymorphisms and biophysical properties, impacting drug effects

    Polymorphisms in SCN5A

    • Propafenone can induce Brugada syndrome ECG patterns in patients with SCN5A polymorphisms
    • Example: R1193Q polymorphism may increase sensitivity to propafenone

    Point Mutations in SCN5A

    • Mutations in the C-terminus of the α subunit, like M1875T, reduce sensitivity to flecainide
    • Heterozygous M1875T mutations associated with familial atrial fibrillation

    Biophysical Diversity in SCN5A

    • Left ventricular and left atrial cardiomyocytes show natural biophysical differences in SCN5A properties
    • These differences may relate to distinct sodium channel subunit protein expression.

    Studying That Suits You

    Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

    Quiz Team

    Related Documents

    Biophysical Properties of Nav1.5 PDF

    Description

    Explore the intricate biophysical properties of the Nav1.5 cardiac sodium channel. This quiz covers its composition, genetic aspects concerning the SCN5A gene, and experimental techniques in cardiac electrophysiology. Deepen your understanding of clinical implications related to genetic polymorphisms in sodium channels.

    More Like This

    Nav1.5 Biophysical Properties and Gating
    24 questions

    Nav1.5 Biophysical Properties and Gating

    ShinyLongBeach6025 avatar
    ShinyLongBeach6025
    Biophysical Properties of Nav1.5
    26 questions

    Biophysical Properties of Nav1.5

    ShinyLongBeach6025 avatar
    ShinyLongBeach6025
    Use Quizgecko on...
    Browser
    Open
    Browser
    Browser