Channelopathies Flashcards
What is an iron channel?
Transmembrane proteins that create a gates, water filled pore to help establish and control membrane potential by modulating the flow of ions between the intracellular and extracelluar environments
What is the type of pump used in neuron action potential?
Na/K ATPase pump
What is pumped out of the cell in a neuronal action potential during repolarization?
Na
What occurs when there is a genetic type of channelopathy?
Loss of function: too little flux
Gain of function: too much flux
What occurs when there is an acquired type of channelopathy?
Acquired disorder, drugs or toxins
If there is a loss of function does that mean cell function is lost?
No
If there is a loss of function in Na/Ca channels what occurs?
Depressed excitability
If there is a loss of function in K channels what occurs?
Enhanced excitability
If there is abnormal depolarization of neuron cells what could happen?
Seizures and epilepsy
What are some gain of function mutations due to Na influx?
Primary erythromelalgia, paroxysmal extreme pain disorder
What is a loss of function mutation due to Na influx?
Channelopathy associated insensitivity to pain
What is the most prevalent genetic disorder in Caucasians?
Cystic fibrosis
What is the most severe symptoms of CF?
Chronic pulmonary infections
Irreversible airways damage
What causes CF?
Mutations in the CFTR (CF transmembrane conductance regulator)
Chloride channel of epithelial cells
Abnormal protein folding prevents normal Cl- influx
What is the pathophysiology behind CF?
Impaired movement of Cl and Na
Less extracell water
Thicker, dehydrated mucus at epithelial surfaces
Impaired ciliary function and airways bacterial clearance
What would a person from CF often suffer from?
Recurrent infections and inflammation
What are some complications of CF?
No absorption of NaCl, gall stones, enzyme retention, infertility (not sterile)
Salty skin, auto-digestion of the pancreas
What are some treatments for CF?
Chest percussion and inhaled hypertonic saline to clear pulmonary secretions
Antibiotics
Pancreatic enzyme development replacement
Nutrition
Lung transplant
What is the main issue with cardiac channelopathies?
Bad channels lead to bad rhythms
Can be lethal (sudden arrhythmic death cases, SIDS)
In a normal heartbeat, what causes excitation/contraction (depolarization)?
Na and Ca channels
In normal heartbeat, what causes relaxations (repolarization)?
K channels
What is Long QT syndrome?
Prolonged repolarization
Inefficient repolarization allows abnormal excitation
What is the most common cause of Long QT syndrome?
K channel loss of function
Maybe gain of function of Na or Ca channels
What drugs may cause long QT syndrome?
Antiarrhythmic drugs (K channel blockers)
What might trigger an arrhythmia?
Swimming, emotional stress, alarms, post-partum
What is the insulin/glycemic control regulated by?
K-ATP channel
What stimulates insulin secretion from pancreatic beta cells?
ATP and and sulphonylureas (SUR1)
How does the K cause insulin levels to decrease?
K channel activity repolarizes cells
Calcium channels close
Lower calcium depresses exocytosis/secretion
What is the mechanism of insulin secretagoges (SUL)?
Stimulate insulin secretion by interacting with the ATP sensitive K channels
Must have functional beta cells
What occurs in a loss of function K-ATP channelopathy?
Hyperinsulinemic hypoglycemia
Loss of function mutation of Kir6.2 or SUR1
What occurs in a gain of function K-ATP channelopathy?
Neonatal diabetes mellitus
Mature onset diabetes of the young (MODY)
