Resting membrane potential-Properties

I. Electricity in animals
1. Basis of membrane potential
2. Measurement of membrane potential
3. Electrical model of a cell membrane
4. Roderick MacKinnon and the K+ channel
5. Whole cell voltage clamping
6. Types of channels in the neuronal membrane
7. Single channels
8. Refractory period

II. Nervous system

1. Composition
a. General aspects
b. Central nervous system
c. Peripheral nervous system
d. The basic unit of the nervous system
2. Types of glial cells
a. In central nervous system
b. In peripheral nervous system
3. The neuron
a. Types of neurons
b. Parts of a neuron
c. Functional types of neurons
 I. Electricity in animals
Whereas electrical currents in a metal wire are conducted by the flow of electrons, electrical currents
across cell membranes are carried by the major inorganic ions of physiological fluids: Ca2+, Na+, K+, Cl−,
and HCO3 - .

Electrical current across cell membranes flows via three unique classes of integral membrane proteins: -ion
channels, -electrogenic ion transporters, and -electrogenic ion pumps

1. Basis of membrane potential

The plasma membranes of most living cells are electrically polarized, as indicated by the presence of a
membrane potential in the range of 100 mV.
Electrically excitable cells such as brain neurons and heart myocytes also use this energy for signalling
purposes. The brief electrical impulses produced by such cells are called action potentials.

2. Measurement of membrane potential

Membrane potentials can be measured with microelectrodes, dyes or fluorescent proteins voltage
sensitive or with multiwell microelectrode array technology
Currents carried by ions across membranes depend on the concentration of ions on both sides of the
membrane, the membrane potential, and the permeability of the membrane to each ion.
The process of ion permeation through the membrane is called electro diffusion because both electrical
and concentration gradients are responsible for the ionic current.

Resting potential of most vertebrate cells is dominated by high permeability to K+ due to the presence of
K+ channels. The resting permeability to Na+ and Ca2+ is normally very low. Skeletal muscle cells, cardiac
cells, and neurons typically have resting membrane potentials ranging from −60 to −90mV. But they are
excitable cells
Excitable cells generate action potentials by transiently increasing Na+ or Ca2+ permeability and thus
driving Vm in a positive direction. A few cells, such as skeletal myocytes, have high permeability to Cl− .

3. Electrical model of a cell membrane

Currents of Na+, K+, Ca2+, and Cl− generally flow across the cell membrane via distinct pathways
The inside of the cell is negative relative to the outside, even though the outside has more chloride. This is
because of the high concentrations of amino acids inside cells that are negatively charged.

The cell membrane is, generally, a bit leaky with regard to both sodium and potassium (in fact, there are
special ‘leak channels’ for potassium). These ions leak through channels a bit, even when the channels are
closed. The balance is constantly being reset by the sodium-potassium pumps, which expend ATP.
 4. Roderick MacKinnon and the K+ channel
Dr. MacKinnon won the Nobel Prize of Chemistry in 2003 for his structural and mechanistic approaches of
potassium ion channels. He studied biophysics of these channels, purification of the protein and its
crystallography and x-ray characterization.

Chloride channels are more complicated, as there are many different types and they are not generally
being used to maintain resting potential of a cell.

5. Whole cell voltage clamping

The patch clamp method and his designer, Dr. Erwin Neher
In this method, one presses onto the cell surface a glass micropipette electrode with a smooth, fire-
polished tip that is ~1 µm in diameter. Applying slight suction to the inside of the pipette causes a high-
resistance seal between pipette and the cell membrane. The piece of sealed membrane is called a patch,
and the pipette is called a patch pipette. Subsequent application of stronger suction causes the patch to
rupture, creating a continuous, low-resistance pathway between the inside of the cell and the pipette. In
this configuration, whole-cell currents can be recorded
The patch clamp technique allows to observe the activity of a single channel and understand its implication
in the current voltage through the membrane. Single channel currents sum to produce macroscopic
membrane currents.

When the current produces a difference of voltage more negative between both sides of the membrane, is
it called hyperpolarization. If the difference of voltage is reduced, making the inside of the cell more
positive, it is known as depolarization. When the cell recovers the initial voltage the process is called
repolarization
 6. Types of channels in the neuronal membrane
Classes of ion channels can be distinguished on the basis of electrophysiology, pharmacological and
physiological ligands, intracellular messengers, and sequence homology

7. Single channels
Single channels can fluctuate between open and closed states. Close channels are not allowing current and are
responsible of the refractory periods of the electrical cells. Open channels are usually the consequence of an
external stimuli.
Cellular communication in the nervous system is based on electrical and chemical signalling events that are
mediated by ion channels. Certain types of cells, including neurons and myocytes, have a remarkable
property called electrical excitability.

8. Refractory period
Period of time during which an excitable cell cannot generate another action potential in response to a
stimulus. It is divided in absolute refractory period, and relative refractory period

Absolute refractory period

Independently of the intensity of the second stimulus, there is not action potential firing. It is due to the
Na+ channel inactivation, in which the conformational configuration cannot reopen. Large-diameter axons
have a brief absolute refractory period and Small diameter axons have even 10 folds longer absolute
refractory periods.
Relative refractory period

Period of time during which a second action potential can be initiated, but only by a stronger-than-normal stimulus.
It coincides with the period when the voltage-gated K+ channels are still open after inactivated Na+ channels have
returned to their resting state

II. Nervous system

1. Composition
a. General aspects
 b. Central nervous system
Includes brain, cerebellum, brain stem and spinal cord
 c. Peripheral nervous system
Forms the peripheral nerves which include:

a. Sensory neurons that arrive to the posterior horn of the spinal cord

b. Motor neurons divided in two systems: voluntary somatic system and autonomic nervous system (sympathetic
and parasympathetic)
 d. The basic unit of the nervous system
The 2 main structures of the nervous system are neurons and glial cells. Neurons receive, integrate and
transmit information trough chemical signals (neurotransmitters) that generate electrical impulses

2. Types of glial cells

There are 10 times more glial cells than neurons in our body
Glial functions include:
a. surround and isolate neurons with a physical support to them as well as delivering of nutrients and
oxygen b. clean up debris as molecules, dead cells or microbia
c. some of them cover the axons with myelin, increasing the speed of transmission of the axon potential

a. In central nervous system

Astrocytes
Are the most abundant glial cells, regulate the internal environment and contribute to blood-brain barrier
Ependymal cells
Line the cavities around the central nervous system, produce cerebrospinal fluid and facilitate its circulation and
provide neuronal stem cells for brain regeneration

Oligodendrocytes
Are the myelinating cells of the central nervous system

Microglia
Immnune defense cells very important in neurodegenerative diseases
 b. In peripheral nervous system

Satellite cells
Small cells that surround neurons in sensory, sympathetic, and parasympathetic ganglia and help to
regulate the external chemical environment

Schwann Cells
Provide myelination to axons in nerves and have phagocytic activity and the capacity to clear cellular debris
that allows for regrowth of PNS neurons
Enteric glial cells
Found in the intrinsic ganglia of the digestive system, they are thought to have many roles in the enteric
system related to reostasis and muscular digestive processes
 3. The neuron
a. Types of neurons

b. Parts of a neuron
The neuron has different parts:
-perikarion, cell body or soma
-dendrites
-axon

The Perikarion is surrounded by the axolemma or plasma membrane

Contains a) the nucleus b) the cytoplasm (axoplam) c) the cytoskeleton
Lipofusin, a type of lipochrome associated with aging, appears in glial and neuronal cells

b) the axoplam has the typical cellular organelles

-mitochondria -Golgi complex -lysosomes -free ribosomes -rough endoplasmic reticulum, termed Nissl
bodies
c) the cytoskeleton
-neurofibrils that provide support and maintain the shape of the cells
-microtubules that help the transport of vesicles from the soma to other parts

Dendrites receptor part of the neurons, where the channels for neurotransmitters are located
Axon prolongation by which the neuronal stimulus is propagated to other cells
Are distinguished:
-axon hillock, cone shape structure richer in receptors and where the signal initiates
-initial segment, portion of the axon in touch with the axon hillock
-side branches or axon collaterals
- synaptic end bulb

c. Functional types of neurons

Sensory neuron
Afferent nerves that send signals from the sensory receptors in skin, eyes, ears, etc or from the somatic sensory
system in the skin and different deep structures to the CNS
Motor neuron
Efferent nerves that transmit commands from the CNS to muscles (motor) or organs (autonomic)

Interneuron
Entirely located in the CNS where they integrate functions