Cell physiology - Action potential

Question 1

What are inward and outward current and their effect?

Answer 1

• Inward
  
  • (+) charge flows into the cell → RMP less negative → depolarization
• Outward
  
  • (+) charge flows out of the cell → RMP more negative → hyperpolarization

Question 2

Properties of action potential

Answer 2

• Stereotypical size and shape
• Propagating
• All-or-none

Question 3

Membrane potential at which the action potential is inevitable

Answer 3

Threshold

Question 4

What happens to the net inward and outward current at threshold potential?

Answer 4

Net inward current > net outward current

↓

Resulting depolarization becomes self-sustaining

↓

Upstroke of the action potential

Question 5

RMP is approximately ____ and is the result of the ____

Answer 5

• • 70 mV, cell negative
• High resting conductance to K+, which drives the membrane potential toward the K+ equilibrium potential

Note: At rest, the Na+ channels are closed and Na+ conductance is low

Question 6

Events in the upstroke of the action potential

Answer 6

Inward current

↓

Depolarization

↓

Rapid opening of the activation gates of the Na+ channel and Na+ conductance of the membrane ↑es

↓

Na+ conductance > K+ conductance

↓

Membrane potential is driven toward (but does not quite reach) the Na+ equilibrium potential of +65 mV

Summary: Rapid depolarization during the upstroke is caused by an inward Na+ current → interior becomes less negative

Question 7

Pharmacologic significance of upstroke

Answer 7

Tetrodotoxin (TTX) and lidocaine block these voltage-sensitive Na+ channels and abolish action potentials

Question 8

In summary, repolarization is caused by

Answer 8

Outward K⁺ current

Question 9

Events in the repolarization of the action potential

Answer 9

• Depolarization also closes the inactivation gates of the Na+ channel (but more slowly than it opens the activation gates); closure of the inactivation gates results in closure of the Na+ channels, and the Na+ conductance returns toward zero
• Depolarization slowly opens K+ channels and increases K+ conductance to even higher levels than at rest
• The combined effect of closing the Na+ channels and greater opening of the K+ channels makes the K+ conductance higher than the Na+ conductance, and the membrane potential is repolarized

Question 10

What is an overshoot and undershoot?

Answer 10

• Overshoot
  
  • brief portion at the peak of the action potential when the membrane potential is positive
• Undershoot (hyperpolarizing afterpotential)
  
  • membrane potential is driven very close to the K+ equilibrium potential

Question 11

Occurs when the cell membrane is held at a depolarized level such that the threshold potential is passed without firing an action potential

Answer 11

Neuronal accommodation or simply, accommodation

Question 12

Explain why muscle weakness occurs in hyperkalemia

Answer 12

Increased extracellular potassium levels

↓

Depolarization of the membrane potentials of cells due to the increase in the equilibrium potential of potassium

↓

This depolarization opens some voltage-gated sodium channels, but also increases the inactivation at the same time

↓

Since depolarization due to concentration change is slow, it never generates an action potential by itself

↓

Accommodation

Question 13

Types refractory period, definition, duration and explanation

Answer 13

• Absolute refractory period
  
  • Period during which another AP cannot be elicited, no matter how large the stimulus
    
    • Almost the entire duration of the AP
      
      • The inactivation gates of the Na+ channels are closed when the MP is depolarized; remain closed until repolarization occurs; no action potential can occur until the inactivation gates open
• Relative refractory period
  
  • An AP can be elicited during this period only if a larger than usual inward current is provided
    
    • From end of the absolute RP until MP returns to the resting level
      
      • The K+ conductance is higher than at rest, and the membrane potential is closer to the K+ equilibrium potential and, therefore, farther from threshold; more inward current is required to bring the membrane to threshold

Memory aid:

• _A_RP - _A_ction potential duration
• _R_RP - _R_ight after action potential to _R_MP

Question 14

Comparison of skeletal, smooth, and cardiac muscles transmission

• Upstroke of action potential
• Presence of plateau
• Duration of action potential
• Excitation–contraction coupling
• Molecular basis for contraction

Answer 14

• Upstroke
  
  • Skeletal
    
    • Inward Na⁺ current
  • Smooth
    
    • Inward Ca²⁺ current
  • Cardiac
    
    • Inward Ca²⁺ current (SA node); inward Na+ current (atria, ventricles, Purkinje fibers)
• Presence of plateau
  
  • Skeletal
    
    • No
  • Smooth
    
    • No
  • Cardiac
    
    • Yes
• Duration of action potential
  
  • Skeletal
    
    • ~1 msec
  • Smooth
    
    • ~10 msec
  • Cardiac
    
    • 150 msec (SA node, atria); 250–300 msec (ventricles and Purkinje fibers)
• Excitation–contraction coupling
  
  • Skeletal
    
    • AP → T tubules
      
      • Ca²⁺ release from nearby SR → increase [Ca²⁺]
  • Smooth
    
    • AP opens voltage-gated Ca2+ channels in cell membrane
    • Neurotransmitters and hormones open IP3-gated Ca²⁺ channels in SR
  • Cardiac
    
    • Inward Ca²⁺ current during plateau of AP
    • Ca²⁺-induced Ca²⁺ release from SR
• Molecular basis for contraction
  
  • Skeletal
    
    • Ca²⁺–troponin C
  • Smooth
    
    • Ca²⁺–calmodulin ↑ myosin light-chain kinase
  • Cardiac
    
    • Ca²⁺–troponin C