02_Membrane Potential_Q and A_Jonathan

Question 1

Note: These questions are not complete because the lecture was mostly review. Please see the notes for additional info.

Answer 1

Note: These questions are not complete because the lecture was mostly review. Please see the notes for additional info.

Question 2

V = IR

Answer 2

V = IR

Question 3

Capacitor is the lipid bilayer. It stores charge.

Answer 3

Capacitor is the lipid bilayer. It stores charge.

Question 4

What are the Nernst Equations?

Answer 4

Eion = RT/ZF ln [ion]out/[ion]in

Eion = 61 log [ion]out/[ion]in (for monovalent ions at 37 degrees C)

Question 5

What are leak channels? What do they do?

Answer 5

• Tandem-pore domain K-selective channels that are constitutively open at rest and are not gated by voltage or ligands
• Primarily esponsible for generating resting membrane potential in neurons

Question 6

How much does the conductance of chloride (Gcl) contribute to the resting potential of neurons? What about muscle cells?

Answer 6

• in neurons the conductance is very low and can be ignored

* in muscle cells, the conductance of Cl is significant and can contribute to channelopathies (eg myotonia congenital)

Question 7

How much does Na conductance contribute to resting membrane potential in neurons and muscle cells? When does Na become significant?

Answer 7

• There are some Na leak channels that cause the cell to depolarize slightly thereby causing the resting potential to become less negative than if reliant on K leak channels alone
• Also, because Na is involved in so many other ion pumps (co- and anti-porters), small perturbations of Na can cause channelopathies due to other ions. (eg hyperkalemic periodic paralysis)

Question 8

What percentage of ATP is dedicated to the Na/K channel in the brain? What about in active nerve cells?

Answer 8

• 24%

* 70%

Question 9

What are cardiac glycosides?

Answer 9

• inhibit the Na/K pump by competitive binding to the K binding site on the outside of the cells

Question 10

What is Ouabain? How does it work?

Answer 10

• a poisonous cardiac glycoside
• formerly used as an ionotropic agent
• blocks the Na/K channel ==> Na builds up in cell ==> stimulates the Na/Ca channel to reverse (usually Na/Ca pumps Na into cell and Ca out of cell) ==> Ca gets pumped INTO the cell ==> cardiac myocytes contract more forcefully (ionotropic)

Question 11

What is a Dystonia?

Answer 11

• Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures.

Question 12

What is Rapid-Onset Dystonia-Parkinsonism (RDP)?

Answer 12

• hereditary
• loss of function in the alpha3 subunit of the Na/K channel
• disrupt neuronal function in the cerebellum ==> thalamus ==> basal ganglia
• Parkinson-like symptoms
• Rapid onset (age 15 to 45 and up to 58) symptoms stabilize and remain constant 4 weeks after onset

Question 13

What is Myotonia?

Answer 13

• Myotonia is a symptom of neuromuscular disorders characterized by the slow relaxation of the muscles after voluntary contraction or electrical stimulation.
• repeated effort is needed to relax the muscles, and the condition improves after the muscles have warmed up.
• prolonged, rigorous exercise may also trigger the condition.
• may have trouble releasing their grip on objects or may have difficulty rising from a sitting position and a stiff, awkward gait.

Question 14

What is myotonia congenita?
What channel is involved?
What are the mechanisms involved?

Answer 14

• Remember, Cl channels effect muscle Vm
• Mutation in the Cl channel subunit (CLCN1)
• Reduced Cl conductance (Cl works to hyperpolarize the cell), so Vm is not restored as fast as it should be
• (normally, high K in the T-tubules is balanced by the high resting Cl conductance (Gcl)
• K accumulates in the T-tubules ==> muscle cells remain depolarized and contracted
• Mutated Cl channels only activate at very positive membrane potentials following the multiple action potentials
• Bouts of myotonia can be triggered by cold, exercise, or fatigue

Question 15

What is Hyperkalemic periodic paralysis (HYPP)?

Answer 15

• In muscle cells
• mutation in voltage-dependent Na channel ==> high serum K from exercise
• The mutation in Na channel opens and stays open (becomes voltage-independent) ==> promotes K efflux and further depolarization
• Loss of resting potential causes inability to respond to nerve signals ==> paralysis