20110103 Lecture 2 notes.txt

From Iusmphysiology

Revision as of 02:28, 6 January 2011 (edit) 149.166.35.72 (Talk) (Created page with '*started here on 01/03/11 at 11AM ===Learning Objectives=== *Understand the nature of the resting membrane potential *Understand the structure & function of ion channels *Und…') ← Older edit		Revision as of 02:30, 6 January 2011 (edit) (undo) 149.166.35.72 (Talk) Newer edit →
Line 23:		Line 23:
	**This makes sense because the net charge difference is high.		**This makes sense because the net charge difference is high.
-	===The Nernst equilibrium potential (Ex) ===	+	===The Nernst equilibrium potential (Ex)===
	*We have two forces: electrostatic force and chemical force.		*We have two forces: electrostatic force and chemical force.
	*RTln ([Xi] / [Xo]) gives the chemical energy.		*RTln ([Xi] / [Xo]) gives the chemical energy.
Line 38:		Line 38:
	*Inhibitors like ouabain and digoxin.		*Inhibitors like ouabain and digoxin.
-	===Kir and K2P channels control the resting potential ===	+	===Kir and K2P channels control the resting potential===
	*We have ion channels that let ions through.		*We have ion channels that let ions through.
	*Human ion channels can either let potassium or na through.		*Human ion channels can either let potassium or na through.
	*Two-pore K+ channels have two pores that are linked as the same protein.		*Two-pore K+ channels have two pores that are linked as the same protein.
-	===Structure of potassium channels	+	===Structure of potassium channels===
-	===	+
	*There are multiple subunits in these pores; each has two transmembrane domains.		*There are multiple subunits in these pores; each has two transmembrane domains.
	*The channel resembles a ?		*The channel resembles a ?
Line 55:		Line 54:
	**Why does it oscillate?  Perhaps this is how we generate thoughts and nerve impulses.		**Why does it oscillate?  Perhaps this is how we generate thoughts and nerve impulses.
-	===Electrotonic spread of depolarization ===	+	===Electrotonic spread of depolarization===
	*So we fish for squids because they have very long axons that have to act quickly to propel the squid forward.		*So we fish for squids because they have very long axons that have to act quickly to propel the squid forward.
	**One milimeter thick axons!		**One milimeter thick axons!
Line 66:		Line 65:
	***spreads in both directions		***spreads in both directions
-	===Length constant ===	+	===Length constant===
	*If you inject at a given point, the adjacent areas are depolarized but the depolarization decays over the length.		*If you inject at a given point, the adjacent areas are depolarized but the depolarization decays over the length.
	*Why does it decay?		*Why does it decay?
Line 75:		Line 74:
	===Stronger depolarizations activated reproducible membrane		===Stronger depolarizations activated reproducible membrane
-	potential changes resembling those seen in vivo ===	+	potential changes resembling those seen in vivo===
	*They found that:		*They found that:
	**If enough K+ is injected to depolarize above a threshold, the neruon goes crazy and generates its own depolarization force.		**If enough K+ is injected to depolarize above a threshold, the neruon goes crazy and generates its own depolarization force.
-	===Self-regenerating squid axon action potential	+	===Self-regenerating squid axon action potential===
-	===	+
	*They showed that neurons show a characteristic change upon depolarization.		*They showed that neurons show a characteristic change upon depolarization.
	*When we exceed the threshold level, (about -55 mV), a polarization peak occurred followed by a repolarization phase.		*When we exceed the threshold level, (about -55 mV), a polarization peak occurred followed by a repolarization phase.
Line 88:		Line 86:
	===Separation of Na+ and K+ currents in squid axon		===Separation of Na+ and K+ currents in squid axon
-	by ionic substitution (voltage-clamp)	+	by ionic substitution (voltage-clamp)===
-	===	+
	*They used a voltange clamp to change the potential to whatever level they wanted.		*They used a voltange clamp to change the potential to whatever level they wanted.
	*First they showed that there is some influx of Na, then some outflux of Na.		*First they showed that there is some influx of Na, then some outflux of Na.
Line 99:		Line 96:
	*Tetra? is a potassium channle inhibitor		*Tetra? is a potassium channle inhibitor
-	===Changes in the permeability to sodium and potassium underlie the shape of the squid axon action potential ===	+	===Changes in the permeability to sodium and potassium underlie the shape of the squid axon action potential===
	*We don't need to memorize the chord conductance equiation.		*We don't need to memorize the chord conductance equiation.
	**Know that it is proportional to the conductance of ?		**Know that it is proportional to the conductance of ?
-	===Membrane topology of voltage-gated cation	+	===Membrane topology of voltage-gated cation===
-	===	+
	*There is an additional domain (s4 transmembrane domain, with positively charged residudes) that sense the voltage.		*There is an additional domain (s4 transmembrane domain, with positively charged residudes) that sense the voltage.
	*There are peptide linkers that connect all the transmembrane domains.		*There are peptide linkers that connect all the transmembrane domains.
-	===Multipolar neuron ===	+	===Multipolar neuron===
	*Na channels are found predominantly along the axon hillock and the axon.		*Na channels are found predominantly along the axon hillock and the axon.
	*Body = soma		*Body = soma
Line 114:		Line 110:
	*In the axon hillock they thought that the triggering of the sodium channels was probably easier than along the axon.		*In the axon hillock they thought that the triggering of the sodium channels was probably easier than along the axon.
-	===Refractory Periods	+	===Refractory Periods===
-	===	+
	*They showed that the action potential can only go one way because of the '''Absolute refracton period'''.		*They showed that the action potential can only go one way because of the '''Absolute refracton period'''.
	*This occurs because the sodium channels are not functional for a short period after depolarization.		*This occurs because the sodium channels are not functional for a short period after depolarization.
	*During hyperpolarization, one can depolarize again, but it takes a greater change in voltage.		*During hyperpolarization, one can depolarize again, but it takes a greater change in voltage.
-	===Multipolar neuron with a myelinated axon ===	+	===Multipolar neuron with a myelinated axon===
	*Schwann cells wrap around the axon to genreate a myelin insulation.		*Schwann cells wrap around the axon to genreate a myelin insulation.
	**Can generate 200 layers around the axon.		**Can generate 200 layers around the axon.
Line 130:		Line 125:
	**Thi sis called '''saltatory conduction'''.		**Thi sis called '''saltatory conduction'''.
-	===Types of the action potential	+	===Types of the action potential===
-	===	+
	*Boards usually have at least one question about shape of action potential.		*Boards usually have at least one question about shape of action potential.
	*In the nodes of ranvier, there is no hyperpolarization because there are no DP K channels.		*In the nodes of ranvier, there is no hyperpolarization because there are no DP K channels.
Line 156:		Line 150:
	*Cross talk between adjacent demyelinated axons		*Cross talk between adjacent demyelinated axons
-	===Nerve conduction testing ===	+	===Nerve conduction testing===
	*We will do a lab about this in TBL with Dr. Kincaid.		*We will do a lab about this in TBL with Dr. Kincaid.
	*We can measure via two electrodes.		*We can measure via two electrodes.
Line 168:		Line 162:
	**So touch is faster than pain.		**So touch is faster than pain.
-	===Summary ===	+	===Summary===
	*Potassium is crucial for resting membrane.		*Potassium is crucial for resting membrane.
	*Influx of sodium through voltage gated Na channels is important for AP generation.		*Influx of sodium through voltage gated Na channels is important for AP generation.

---

Revision as of 02:30, 6 January 2011

• started here on 01/03/11 at 11AM

Contents 1 Learning Objectives 2 Ion concentration in mammalian neuronal cells 3 In a liposome 4 The electrical field on the plasma membrane is IV 175 kV/cm 5 The Nernst equilibrium potential (Ex) 6 NA+, K+ ATPas (NA/K Pump) 7 Kir and K2P channels control the resting potential 8 Structure of potassium channels 9 Multipolar neuron 10 Electrotonic spread of depolarization 11 Length constant 12 Self-regenerating squid axon action potential 13 Changes in the permeability to sodium and potassium underlie the shape of the squid axon action potential 14 Membrane topology of voltage-gated cation 15 Multipolar neuron 16 Refractory Periods 17 Multipolar neuron with a myelinated axon 18 Types of the action potential 19 Demyelinating disorders 20 Demyelination consequences 21 Nerve conduction testing 22 Conduction velocity in peripheral sensory and motor axons 23 Summary

Learning Objectives

• Understand the nature of the resting membrane potential
• Understand the structure & function of ion channels
• Understand passive/electrotonic conduction

• Understand the mechanisms underlying action potential generation & propagation
• Understand how myelination affects action potential propagation

Ion concentration in mammalian neuronal cells

• Potassium is high in cells, low in ECF.
• Sodium is low in the cell and high outside the cell.

In a liposome

• Because of trends toward disorder so ions always want to be in equal molar concentration on either side of a membrane.
• If we let out a positive ion, then we build up negative potential inside the cell.

The electrical field on the plasma membrane is IV 175 kV/cm

• The ions will line up along the membrane because the potential causes them to attrack even across the membrane distance.
  • The membrane is only 4 nanometers thick
  • This makes sense because the net charge difference is high.

The Nernst equilibrium potential (Ex)

• We have two forces: electrostatic force and chemical force.
• RTln ([Xi] / [Xo]) gives the chemical energy.
• The electrical force is given by zxFV_m
• At equilibrium these two forces sum to zero
• This gives us the Nernst equation: Vm = (RT / ZxF) * ln [Xo] / [xi]
  • Simplifies to Ex = 61.54 / Zx * Log [x0] / [xi]
  • Memorize this because it is sometimes on boards (?).
• A cell usually has a potential of about -70 mV.

NA+, K+ ATPas (NA/K Pump)

• Pumps 3 Na+ out and 2 K+ in.
• Burns 1 ATP per cycle.
• Inhibitors like ouabain and digoxin.

Kir and K2P channels control the resting potential

• We have ion channels that let ions through.
• Human ion channels can either let potassium or na through.
• Two-pore K+ channels have two pores that are linked as the same protein.

Structure of potassium channels

• There are multiple subunits in these pores; each has two transmembrane domains.
• The channel resembles a ?
• The D loop is important for determine the selectivity of the channel (for an ion like K+).

Multipolar neuron

• Neurons have: body, dendrites, nucleus, axon hillock (the initial segment of the axon), axon, and nerve terminals.
• If we put an electrode in, the potential is -70 mV again.
• But if we do the experiment in vivo we would find that the resting potential is not stable, is pulses.
  • Why does it oscillate? Perhaps this is how we generate thoughts and nerve impulses.

Electrotonic spread of depolarization

• So we fish for squids because they have very long axons that have to act quickly to propel the squid forward.
  • One milimeter thick axons!
• They poked electrodes into the axons and studied the K+ ions.
• They injected potassium into the axons.
• They found that the depolarization could spread along the axon.
  • Sweet, this is probably how neurons work in vivo.
  • We call this passive depolarization.
  • The ions don't travel the lengths of the axons, they just displace their neighbor and this occurs all the way down the axon.
    • spreads in both directions

Length constant

• If you inject at a given point, the adjacent areas are depolarized but the depolarization decays over the length.
• Why does it decay?
  • Because there is some resistance.
  • Because their
  • The decay is proportional to the square root of the diameter times the Resistance(M) over twice the R(a)

What is R(a)

===Stronger depolarizations activated reproducible membrane potential changes resembling those seen in vivo===

• They found that:
  • If enough K+ is injected to depolarize above a threshold, the neruon goes crazy and generates its own depolarization force.

Self-regenerating squid axon action potential

• They showed that neurons show a characteristic change upon depolarization.
• When we exceed the threshold level, (about -55 mV), a polarization peak occurred followed by a repolarization phase.
• The depolarization is due to the inrush of Na+. (?)
• Hyper repolarization reaches down to E_k
  • This is due to the inrush of K+

===Separation of Na+ and K+ currents in squid axon by ionic substitution (voltage-clamp)===

• They used a voltange clamp to change the potential to whatever level they wanted.
• First they showed that there is some influx of Na, then some outflux of Na.
• Then they removed Na from the ECF and showed that there was no influx of Na.
• Then they removed Na from the intracellular space and showed that there was no Na outflux.
• These were done to confirm their experiments.
• They showed taht these channels functioned by changes in voltage so they called them voltage-gated channels.
• Tetrodotoxin inhibits voltage-gated Na channels.
• Tetra? is a potassium channle inhibitor

Changes in the permeability to sodium and potassium underlie the shape of the squid axon action potential

• We don't need to memorize the chord conductance equiation.
  • Know that it is proportional to the conductance of ?

Membrane topology of voltage-gated cation

• There is an additional domain (s4 transmembrane domain, with positively charged residudes) that sense the voltage.
• There are peptide linkers that connect all the transmembrane domains.

Multipolar neuron

• Na channels are found predominantly along the axon hillock and the axon.
• Body = soma
• Concentration of na channels are lower in body and ?
• In the axon hillock they thought that the triggering of the sodium channels was probably easier than along the axon.

Refractory Periods

• They showed that the action potential can only go one way because of the Absolute refracton period.
• This occurs because the sodium channels are not functional for a short period after depolarization.
• During hyperpolarization, one can depolarize again, but it takes a greater change in voltage.

Multipolar neuron with a myelinated axon

• Schwann cells wrap around the axon to genreate a myelin insulation.
  • Can generate 200 layers around the axon.
• This insulation blocks the currents (?).
• The schwann cells leave 2 micrometer gaps called the nodes of ranvier.
• The density of the sodium channels at the nodes is very high but there are no delayed reaction K+ channels.
• The major advantage of myelination is that it speeds up depolarization.
  • This is because without myelination you have to depolarize every channel along the way but with myelination you let the ions bump along in the axon to the next channel where depolarization occurs.
  • Thi sis called saltatory conduction.

Types of the action potential

• Boards usually have at least one question about shape of action potential.
• In the nodes of ranvier, there is no hyperpolarization because there are no DP K channels.
• The AP decays because Na channels become deactivated.
• Spaced out.

Demyelinating disorders

• MS:
  • Central neruons affected
  • Loss of motor control
• Guillain-Barre' syndrome
  • peripheral nerves are affected
  • associated with shots / immunizations
• CMT
  • genetic in etiology
• Krabbe's disease
  • Genetic in etiology

Demyelination consequences

• Decreased propagation velocity
• Only a fraction of high-frequency spikes propagate
• Total blockade
• Ectopic spike generation (decreased threshold or mechanical sensitivity)
• Cross talk between adjacent demyelinated axons

Nerve conduction testing

• We will do a lab about this in TBL with Dr. Kincaid.
• We can measure via two electrodes.
• We excite the nerve at the elbow and wrist and look at the spikes (called compound action potential, because it is usually comeing through multiple fibers).
• By measuring the delay, we can divide the length by time and get the velocity.

Conduction velocity in peripheral sensory and motor axons

• Don't need to memorize these
• Can be up to 120 meters / second (skeletal muscle).
• Pain is transmitted very slowly, though.
  • So touch is faster than pain.

Summary

• Potassium is crucial for resting membrane.
• Influx of sodium through voltage gated Na channels is important for AP generation.
• Different cells have different shaped APs.
  • The shape is a function of the expression pattern of Na and K channels in the cell.
• The velocity depends on the diameter of the myelinated axon.

• stopped here on 01/03/11 at 12PM