Resting Membrane Potential

Give two examples on how galvanic current could be used as a therapeutic device

1. Iontophoresis

   • use of direct current to drive an ionized drug through the skin

   • Transdermal drug delivery

   • mild electrical current

2. Pain management

   • Direct current blocks nocioceptive signals

   • current “overwhelms” the small diameter pain fibers (C fibers) → Shuts gate in spine 

Describe the gate control theory of pain management

Normally: stimulation of C fibers stimulates the projection neurons in the dorsal horn and thus sends the pain signals on to the brain (A)

Applying an electrical current to the area in pain does the following:

• Activation of the inhibitory interneurons and larger Aβ fibers → stops nocioceptive signals

• Pressure (massage) can also do this by activating the large diameter Aβ fibers

What is the membrane potential necessary for? how is this Charge differential created?

• necessary for signaling (particularly in neuromuscular systems)

• Potential created via movment of ions through protein carriers 
  

What are the four types of ion channels?

• Voltage gated channels

  • Common: Na, K, Ca

  • Open due to change in membrane voltage

• Ligand-gated channels

  • Binds ligand to open (ex: Acetylcholine)

• Constitutively open

  • “leak” channels

  • Na, K

  • EnaC: epithelial sodium channels

• Gap Junction

  • Near-instantaneous transmission of signal

  • open via change in voltage, pH or Ca ions

  • Ex: Intercalated discs in cardiac muscle

Describe the different structures of the different ion channels

• Central Pore

• Different subunits for different ion channel function

  • Voltage gated: 4 subuints

  • Ligand gated: 5 subunits

  • Gap junction: 6 subunits

  • ENaC channel: 3 subunits

Describe the mechanism for depolarization and repolarization of action potential

• Depolarization

  • opening of voltage-gated sodium channels → Na enters → more positive cell
    

• Repolarization

  • Closure of voltage-gated sodium channels; Opening of voltage-gated potassium channels → K leaves cell → more negative cell
    

What is equilibrium potential? What formula do we use to calculate this?

• Equilibrium potential: The voltage at which each individual ion prefers the cell

• We use the Nernst Equation to calculate this

What is the equilibrium potential of Na and K? Explain the logistics for these equilibrium potentials

K: - 95; potasium [] is high inside; low outside; thus it wants to go out

Na: + 67; Na [] is high outside; low inside; thus it wants to go in

Why is the membrane potential of neuron cells extremely similar to K+ equilibrium potential at rest?

• This is because potassium has the most conductance at rest (80-100 % of conductance is by K+)

  • This is because K+ channesl are “leak” channels whilst Na+ channels are voltage gated

    • Thus, K+ channels are always open 

What happens if we add K+ into the extracellular environment? What happens if we remove K+ from extracellular environment?

• Add: 

  • Cell depolarizes due to reduced K+ movement out

• Remove:

  • Cell hyperpolarize due to increased K+ out

What is the Goldman equation? Based on this equation? What are the three factors that dictate membrane potential

• Gives a cell’s membrane potential; espeically when its membarne is permeable to several ions

• Factors that dictates membrane potential

  • Polarity (direction) of each ion

  • Concentration difference across membrane for each ion

  • Permeability of membrane to each ion

What is Ohm’s Law?

I=V/R or I = VxG

I= current

V= voltage

R = resistence

G = Conductance

What are the main ions that dictate membrane potential for:

Skeletal muscles/nerve?

Smooth muscles?

Respiratory tracts?

• Muscles/nerves: K/Na

• Smooth muscles: Ca/K

• Respiratory tract: Mucous secretions

Define the Electrochemical Driving Force

• Difference between the actual membrane potential (Vm) and the equilibrium potential (Veq) for a given ion
  

• Net driving force (Vdf) = Vm-Veq

What is the movement of ions depended on? What is conductance dependent on?

• Dependent upon both driving force and ionic conductance

• Conductance: Determined by ion channel number and probability that it is open

How do we measure membrane potential?

• One electrode filled with an electrolyte solution

  • impaled through the cell membrane into the interior of the fiber
    

• Another is in the extracellular fluid space

  • The “indifferent electrode”
    

• Measures the voltage difference on either side of the membrane

Besides the ECF of Na/K? What is another contributor to resting membrane potential?

• Na-K ATPase pump

• Small contributor; makes interior -4mV

  • Small leakage of Na into the cell; Pumps pump those Na out (3:2 ration; 3Na for 2K)