2022-02-03 07:31:17

Prelude (4:20)

Prelude (2:33)

Announcements

  • Exam 1 Thursday, 2/10
    • 40 questions
    • No in-person/in-class meeting
    • On Canvas, live at 3:05 PM; open until 10:00 PM

Today’s Topics

  • Electrical communication in neurons
  • The action potential

How do neurons communicate?

Types of neural electrical potentials

  • Resting potential
    • Voltage across neuronal membrane when cell is ‘at-rest’ (not firing)
  • Action potential
    • Voltage across neuronal membrane when cell is active or firing

Where does the resting potential come from?

  • Ions (charged particles)
  • Ion channels
  • Separation between charges
  • A balance of forces

We are the champIONs, my friend

  • Potassium, \(K^+\)
  • Sodium, \(Na^+\)
  • Chloride, \(Cl^-\)
  • Organic anions, \(A^-\)

Party On

  • Annie (\(A^-\)) was having a party.
    • Used to date Nate (\(Na^+\)), but now sees Karl (\(K^+\))
  • Hired bouncers called
    • “The Channels”
    • Let Karl and friends in or out, keep Nate out
  • Annie’s friends (\(A^-\)) and Karl’s (\(K^+\)) mostly inside

  • Nate and friends (\(Na^+\)) mostly outside
  • Claudia (\(Cl^-\)) tagging along

Resting potential arises from

  • A balance of forces
    • Force of diffusion
    • Electrostatic force
  • Forces cause ion flows across membrane
    • Force of diffusion consistent (over time)
    • Electrostatic force changes
  • Ion channels allow ion flow

Ion channels

  • Openings in neural membrane
  • Selective for specific ions
  • Vary in permeability (how readily ions flow)
  • Types
    • Passive/leak (always open)
    • Voltage-gated
    • Ligand-gated (chemically-gated)
    • Transporters/pumps

Ion channels

Neuron at rest permeable to \(K^+\)

  • Permeable: Permits flow across/through
  • Passive \(K^+\) channels open
  • [\(K^+\)] concentration inside >> outside
  • \(K^+\) flows out
    • Neuron constantly brings \(K^+\) in

Force of diffusion

Force of diffusion

Neuron at rest permeable to \(K^+\)

  • Organic anions (\(A^-\)) too large to move outside of cell
  • \(A^-\) and \(K^+\) largely in balance == no net internal charge
  • \(K^+\) outflow creates charge separation: \(K^+\) (outside) <-> \(A^-\) (inside)
  • Charge separation creates a voltage
  • Outside +/inside -
  • Voltage build-up stops outflow of \(K^+\)

The resting potential

Balance of forces in the neuron at rest

  • Force of diffusion
    • \(K^+\) moves from high concentration (inside) to low (outside)

Balance of forces in the neuron at rest

  • Electrostatic force
    • Voltage build-up stops \(K^+\) outflow
    • Specific voltage that stops flow == equilibrium potential for \(K^+\)+
    • \(K^+\) positive, so equilibrium potential negative (w/ respect to outside)
    • Equilibrium potential close to neuron’s resting potential

Equilibrium potential and Nernst equation

Equilibrium potentials calculated under typical conditions

Neuron resting potential ≠ \(K^+\) equilibrium potential

  • Resting potential not just due to \(K^+\)
  • Other ions flow
  • Resting potential == net effects of all ion flows across membrane

Goldman-Hodgkin-Katz equation

\(Na^+\) role

  • \(Na^+\) concentrated outside neuron
  • Membrane at rest not very permeable to \(Na^+\)
  • Some, but not much \(Na^+\) flows in
  • \(Na^+\) has equilibrium potential ~ + 60 mV
  • Equilibrium potential is positive (with respect to outside)
  • Would need positive interior to keep \(Na^+\) from flowing in

Electrical circuit model

Summary of forces in neuron at rest

Ion Concentration gradient Electrostatic force Permeability
\(K^+\) Inside >> Outside - (pulls \(K^+\) in) Higher
\(Na^+\) Outside >> Inside - (pulls \(Na^+\) in) Lower

What happens if something changes?

  • Easier for Karl [\(K^+\)] to exit?
  • Easier for Nate [\(Na^+\)] to enter?
  • Some action!

Action potential

Phases of the action potential

  • Threshold of excitation
  • Increase (rising phase/depolarization)
  • Peak
    • at positive voltage
  • Decline (falling phase/repolarization)
  • Return to resting potential (refractory period)

Action potential break-down

Phase Neuron State
Rise to threshold + input makes membrane potential more +
Rising phase Voltage-gated \(Na^+\) channels open, \(Na^+\) flows in
Peak Voltage-gated \(Na^+\) channels close and deactivate; voltage-gated \(K^+\) channels open
Falling phase \(K^+\) flows out
Refractory period \(Na^+\)/\(K^+\) pump restores [\(Na^+\)], [\(K^+\)]; voltage-gated \(K^+\) channels close

What’s a \(Na^+\)/\(K^+\) pump?

  • Enzyme – \(Na^+\)/\(K^+\) ATP-ase – embedded in neuron membrane
  • Pumps \(Na^+\) and \(K^+\) against concentration gradients
  • \(Na^+\) out; \(K^+\) in
  • Uses adensosine triphosphate (ATP) form of chemical energy

Example in another domain

Refractory periods

  • Absolute
    • Cannot generate action potential (AP) no matter the size of the stimulus
    • Voltage-gated \(Na^+\) channels inactivated, reactivate in time.

Refractory periods

  • Relative
    • Can generate AP with larg(er) stimulus
    • Some voltage-gated \(K^+\) channels still open
  • Refractory periods put ‘spaces’ between APs

Generating APs

  • Axon hillock
    • Portion of soma adjacent to axon
    • Integrates/sums input to soma
  • Axon initial segment
    • Umyelinated portion of axon adjacent to soma
    • Voltage-gated \(Na^+\) and \(K^+\) channels exposed
    • If sum of input to soma > threshold, voltage-gated \(Na^+\) channels open

Axon hillock, axon initial segment

Nodes of Ranvier

  • Regenerate action potential
  • \(Na^+\) and \(K^+\) channels exposed to extracellular environment
  • Between Nodes of Ranvier, ions can’t move out, so move along
  • Nodes of Ranvier -> Action potentials faster & reliable for a given diameter

Main points

  • Resting potential maintained by balance of forces (diffusion, electrostatic)
  • Action potential generated when balance is altered
    • \([Na^+]\) in: rising phase to + peak
    • \([K^+]\) out: falling phase

Next time

  • More on the action potential
  • Review for Exam 1

References