Intro + CNS Control 1 Excitable Cells

Which of the following changes in extracellular ion concentrations would decrease the excitability of a neuron by moving its resting membrane potential further away from the threshold for an action potential

• An increase in extracellular potassium concentration ([K+]O)

• A decrease in extracellular potassium concentration ([K+]O)

• A decrease in extracellular sodium concentration ([Na+]O)

• An increase in extracellular sodium concentration(Na+]O)

• A decrease in extracellular calcium concentrations ([Ca++]O)

Question 1 explained

• Decreasing the excitability makes it harder to get an AP

• If RMP reaches threshold → AP

• If RMP moves further from threshold → harder to get an AP, takes more effort, cell is less excitable

• Intracellular could be a factor to RMP, but we don’t care because intracellular doesn’t change (super stable, not stable → patient is sick)

  • Body can’t regulate intracellular fluid

  • Assumes that if EC is good, IC is good

• Cell membrane isn’t that permeable to Na+, very permeable to K+ (at rest, 20-30x more)

• EC Ca++ is a stabilizer, helps determine where threshold is

• EC K+ most influential on RMP

• More K+ inside the cell, concentration gradient for K+ inside got smaller when we increase EC K+

  • If K+ wants to move out of the cell and the gradient is smaller, less K+ moves out of cell → cell remains more positive, RMP goes up

• Answer B: made it bigger, K+ is more likely to leave cell → cell becomes more (-)

Anatomy of a neuron

An Action Potential

• All cells of the body have a (-) charge on the inside of the membrane

• RMP is a balance between E Na+and E K+

Establishment

• Uneven distribution of ions across plasma membrane (uneven distribution/permeability)

  • More sodium outside the cell than in

  • More potassium inside the cell than out

  • Large intracellular proteins

    • can’t leave the cell

    • have negative charge (large anionic proteins)

Differential Permeability

• Under resting conditions

  • Membrane 25 to 30 times more permeable to K+ than Na+

  • K+ wants to diffuse down its gradient

  • Yet, K+ is attracted to the negative charges on the proteins

  • A balance between these two opposing desires is struck, called the Equilibrium Potential (E K+) of potassium

    • Net movement of K+ is 0

    • (-) charge of A- proteins perfectly balances the concentration gradient

  • Just because K+ leaves the cell, we are not depleting the IC K+ level at all

    • not losing enough to interfere with IC, stays constant

Potassium Concentration Gradient

• (+) and (-) are balanced

  • hypothetically

Movement of Potassium

• As K+ goes out, (-) charge is no longer balanced

• Electrical gradient →

  • slight inward charge that is (-)

  • ex: 30 (-) & 29 (+) inside

    • neg. pull

    • gets stronger as K+ leaves

Balanced Potassium

• Balanced perfectly at equilibrium

  • E K+ -90mV

• Every 1 K+ that goes out of cell 1 comes in

Equilibrium Potential

• Calculated by the Nernst Equation

  • ONLY solves for equilibrium

  • Deals with equilibrium potential of (1) ion

• Equilibrium potential is based on concentration gradient, permeability not part of

  • Only deals with 1 ion

    • Given this concentration gradient, how strong does (-) charge need to be to balance it?

    • EC

• K+

  • if extracellular concentration goes down, it becomes more (-)

  • if extracellular concentration goes up, it becomes less (-)

    • concentration gradient becomes smaller, less K+ is leaving

    • cell stays (+)

• Na+

  • at 61 mV E= 61 log (150/15)

  • net movement of Na+ is 0

• Permeability does NOTHING to this

Movement of sodium

• 10:1 ratio

  • Concentration and electrical gradients tells Na+ to go in

Movement of Sodium (2)

• As Na+ goes in, electrical gradient gets smaller

Sodium Equilibrium Potential

• If enough Na+ comes in, electrical gradient will flip

• Ex: Chipotle free burritos

  • long line → people leave/don’t wait in line

Resting Membrane Potential

• Na+ has an equilibrium potential

• Combination of both E K+ and E Na+

  • Contributes to the overall membrane potential

  • Heavily weighted toward E K+ due to the increased permeability of the membrane to K+ as compared to Na+

    • Gives votes based on permeability

    • 25:1

• Average resting membrane potential = ~-70 mVolts

  • Follows K+ equilibrium potential, more influential

All ions at Equilibrium

• K+

  • concentration gradient for K+ tends to move it out of cell

  • outside of cell becomes more (+)

  • inside of cell becomes more (-), membrane impermeable to A-

  • electrical gradient: K+ in

• Na+

  • Na+ in

  • outside becomes more (-) with Cl-

  • electrical gradient moves Na+ out

• E K+ = -90 mV

• E Na+ = 61 mV

Clinical Minute

• Seizure focus

  • Region(s) of the brain are hyperexcitable (too close to threshold, too positive)

    • Randomly firing

• What strategies can we use to decrease the excitability of these regions?

Influences on RMP

• Increase ECF K+

  • Concentration gradient for K+: less/smaller

  • K+ leaves cell less, becomes more (+)… excitable

  • Not good treatment for epilepsy

• Decrease ECF K+

• Increase K+ permeability

  • Goldman equation, “vote”

• Decrease K+ permeability

• Increase Na+ permeability

  • Permeability: increase # of votes Na+ gets

  • Wants 61 (equilibrium potential)

  • RMP goes up, more likely to hit AP

  • NOT good for seizures!

• ICF is constant

• Concentration → Nernst, equilibrium potential

Nernst Equation (for equilibrium potentials)

• Based upon concentration gradient

  • Ratio

• Physiologically - ECF

GHK Equation (for RMP)

• Influenced by

  • Concentration gradient

  • Permeability

Background Information

• RMP is not constant

  • Variations initiated by external signals can be called “graded potentials”

• Graded potentials may result in action potentials (does it cause an AP or not)

Graded Potentials vs. Action Potentials

Graded Potentials

• Local changes

  • Usually at the dendrites

    • Channels (channels responsible for graded potential are different than channels responsible for AP. Ligand-gated: external signal)

  • Decremental

    • Die-out (once they start)

    • Not propagated (sent forward)

  • Varying amplitude (can be strong or weak)

  • Varying duration

Action Potentials

• Span entire membrane

  • Axon

    • Axon hillock

  • Non-decremental

  • Channels

    • Voltage-gated

  • Constant amplitude

  • Constant duration

Polarizations

• APs → depolarize

• Graded Potentials → hypo

Comparison of Graded Potentials to Action Potentials

Action Potentials

• Polarity (RMP)

• Threshold

  • Caused by graded potentials (strong enough to push RMP to threshold value)

  • Point at which voltage-gated channels open (detect change)

• Depolarization

  • Opening of voltage-gated Na+ channels

  • Rapid influx of Na+

• Repolarization

  • Rapid efflux of K+

• Hyperpolarization

  • Slow closure of voltage-gated K+ channels

Role of Voltage-Gated Sodium Channels

Types of Graded Potential

• Excitatory (hypopolarizing)

  • Influx of Na+

    • Small efflux of K+

• Inhibitory (can stop an AP)

  • Influx of Cl- (cause cell to become more (-))

  • Efflux of K+

Grand Post Synaptic Potential (EPSPs + IPSPs)

• Summation

  • Stacking of graded potentials

    • Graded potentials do not have an absolute refractory period (not dealing with V.G. channels)

  • May result in the formation of an action potential

• Spatial

• Temporal

Clinic Minute: Benzodiazepines

• Anxiety is associated with specific neurons in the limbic system

  • Gabaminergic

• Benzos potentiate GABA

• How do we have receptors in our brain for benzos?