Lecture 2 - Neural Tissue and Membrane Potentials

Central nervous system (CNS)

Brain, spinal cord

Peripheral nervous system (PNS)

• Sensory/Somatic

• Autonomic

  • Sympathetic (fight or flight)

  • Parasympathetic (rest and digest)

Neuron

Basic functional unit of the nervous system

• dendrite

• axon

• initial segment

Dendrites

receive information via neurotransmitters

Axons

Conduct action potentials, send signals towards axon terminals

Initial segment (axon hillock)

– AP trigger zone

Glial cells

• Supporting cells of CNS and PNS

• Constitute ~90% of cells in CNS (~50% volume)

• Surround the soma, axon, and dendrites of neurons

• Provide physical and metabolic support and much more

Astrocytes

• Spatial buffering of extracellular K+

• Neurotransmitter uptake and release

• Provide metabolic support to neurons

• Guide neuronal migration in developing brain

• Promote myelinating activity of oligodendrocytes

• Mediate neurovascular coupling

• Modulation of synaptic activity

• Nervous system repair

Oligodendrocytes

• Myelinate multiple CNS axons, provide trophic support

• Myelin composed of highly compacted layers (20- 200) of modified PM

• Compact myelin speeds up conduction

  • Electrical insulator

Nodes of Ranvier

Spaces between adjacent sections of myelin - axon’s PM exposed to ECF → saltatory conduction

Schwann Cells

• Myelinate PNS axons.

• Nuclei closely apposed to axon

• Pain and temperature fibers are unmyelinated

• Non-myelinating SCs can myelinate if triggered by neurons

Microglia

Macrophage-like cells that reside in the CNS; proliferate and activate in response to injury

Ependymal cells

Line the fluid filled cavities of the brain; produce CSF

Anterograde axonal transport

• Towards dendrite

  • Synaptic proteins

  • Neurotransmitters

  • Certain mRNAs

Retrograde axonal transport

• Towards cell body

  • Growth factors

Functional classes of neurons

• Groups of afferent and efferent neurons form the nerves of the PNS (they are all bundled together).

• Note that a nerve fiber is a single axon, and a nerve is a bundle of axons

Synaptic inputs

• Axo-dendritic, axo-somatic and axo-axonic

• A single neuron can be postsynaptic to one cell and presynaptic to another cell

Presynaptic

A neuron that conducts a signal towards a synapse

Postsynaptic

One that conducts signal away from the synapse

Electrical potential

Separate charges have the ability to do work

Potential differences

Difference in charge between 2 points, measured in volts

Current

Movement of electrical charge

Ohm’s law

Current proportional to the potential differences and inversely proportional to the resistance (hindrance to charge flow)

I=(V/R)

Insulator

Substance with high electrical resistance

Conductor

Substance with low electrical resistance

Summary: Na+/K+ ATPase

• The Na+/K+ ATPase establishes concentration gradients of Na+ and K+ across the plasma membrane (high Na+ outside and high K+ inside)

• Recall that the pump uses up to 40% of the ATP produced by the cell

• At a steady state, ion fluxes through “leak” channels and activity of the pump balance each other

Distribution of Ions in a Nerve Cell

• Na+, K+ and Cl- are present in the highest concentrations - membrane permeability to each is independently determined.

• Remember: Na+ Cl- out, K+ in

• There are many other ions, including Mg2+, Ca2+, H+, HCO3-, HPO42-, SO42-, amino acids, and proteins in ICF and ECF

Consider a membrane that is permeable only to K+:

a) No potential difference because (+) and (-) ions are equal and channels are closed.

b) If K+ channels open, K+ will diffuse from C2  C1

c) C1 will have an excess of (+) charges and C2, an excess of (-) charges.

d) Additional charge separation

e) The buildup of (+) charges in C1 and (-) charges in C2 produces an electrical potential that exactly offsets the [K+] gradient.

• The membrane potential at which the K+ flux due to the concentration difference becomes equal in magnitude but opposite in direction to the K+ flux due to charge separation is called the K+ equilibrium potential.

In this experimental setup...

• What happens if we increase [K+] in C2? → equilibrium potential will need to be greater

• What happens if we increase [Na+] in C1? → nothing would happen (Na independent, unless it affects electrical potential)

Consider a membrane that is permeable only to Na+:

a) No potential difference because (+) and (-) ions are equal and channels are closed.

b) If Na+ channels open, Na+ will diffuse from C1  C2

c) C2 will have an excess of (+) charges and C1, an excess of (-) charges.

d) Additional charge separation

e) The buildup of (+) charges in C2 and (-) charges in C1 produces an electrical potential that exactly offsets the [Na+] gradient.

• The membrane potential at which the Na+ flux due to the concentration difference becomes equal in magnitude but opposite in direction to the Na+ flux due to charge separation is called the Na+ equilibrium potential.

In this experimental setup...

• What happens if we increase [Na+] in C1? → increase equilibrium/ electrical potential needed

• What happens if we increase [K+] in C2? → no effect

The Nernst Equation

• Describes the equilibrium potential for any ion species

  • The electrical potential necessary to balance a given ionic concentration gradient across a membrane so that the net flux on that ion is zero

Eion = 61/Z log (Co/Ci)

Where,

Eion = equilibrium potential in mV

Ci = intracellular ion concentration

Co = extracellular ion concentration

Z = valence of the ion

61 is a constant that takes into account the universal gas constant, the temperature, and the Faraday electrical constant

The Resting Membrane Potential Charge

• A voltmeter measures a potential difference across the membrane of a resting neuron (millivolts) of –70 mV.

• ECF assigned a voltage of zero

• If the potential across membrane is 70 mV and the cytoplasmic side of membrane has excess negative charge, then the membrane potential is -70 mV

Resting membrane voltages range from _________ in different cells. The membrane is said to be ________

• –50 to – 100 mV

• polarized

Membrane potential determined by two factors:

1. Differences in ionic composition of ICF and ECF

2. Differences in plasma membrane permeability to each ion

Charge Separation Across the Plasma Membrane

• Voltage occurs only at membrane surface

• Tiny excess of (-) ions along the inner surface of the PM and (+) ions around the outside.

• Excess charges collect at plasma membrane and are attracted to each other.

• The bulk of the ECF and ICF remains electrically neutral.

• The actual number of charges that are separated is infinitesimally small compared to total number of charges in the cell.

• Only a very thin shell of charge difference is needed to establish a membrane potential

Leak channels generate what?

Resting potential

Leak channels

• Integral membrane proteins that are selective ion channels - some always open.

• In an actual neuron at rest, there are many more open K+ leak channels than Na+ leak channels.

• So PM is 25 times more permeable to K+ than Na+

• This bring RMP closer to the K+ equilibrium potential

• Therefore, the RMP depends mostly on [K+]. Clinically relevant. – Na+/K+ ATPase maintains resting membrane potential by maintaining concentration gradients

Forces Influencing Na+ and K+ at Rest

• At a resting membrane potential of -70 mV both the concentration gradient and electrical potential favor inward movement of Na+, while the K+ concentration gradient opposes the electrical potential.

• The greater permeability and movement of K+ maintains the resting membrane potential at a value near Ek.

The Goldman-Hodgkin-Katz Equation

• How do we calculate the membrane potential if more than one type of channel is open?

• We need to consider the permeability (P) for each ion species (how many channels are open) and the concentration difference.

• The GHK equation is essentially a modified form of the Nernst equation that takes into account the individual ion permeabilities.

• Vm = 61 log {PK[Ko] + PNa[Nao] + PCl[Cli]} / {PK[Ki] + PNa[Nai] + PCl[Clo]}

• Note that for chloride, [Cli] is in the numerator instead of the denominator. This is because it is a negatively charged ion

E(Na+)

61/1 log (145/15) = +60 mV

log>1 = +#

E(K+)

61/1 log (5/150) = -90 mV

log<1 = -#