Ion Channels and Neuronal Signaling

• Neurons use a combination of electrical and chemical signals to communicate

Ions

• Ions are elements or molecules which are charged
• Ions can be postive (+) or negative (-)
• The movement of ions is how neurons change their voltage/electrical potential

Major Ions for Neuron Signaling

• Sodium: Na+
• Potassium: K+
• Chloride: Cl-
• Calcium: Ca2+

Ion Concentrations

• Ion concentration is not equal inside and outside of the cell, creating an imbalance
• The imbalance in ion concentration is called a concentration gradient
• Concentration gradients are the major driving force for electrical signaling
• Neurons are like "bananas in the sea", or containters of K+ in a solution of salt (Na+ & Cl-), and also Ca2+

Membranes

• Cellular membranes do not allow ions to move in and out of the cell
• Ions depend on specialized proteins called “channels” to pass across the membrane

Ion Channels

• Channels are proteins that are folded into a spiral that leaves a pore in the middle for ions to travel through
• Electrical signaling in neurons is primarily controlled by the opening and closing of channels
• Channels are specific: for example, Na+ can only pass through Na+ channels
• K+ will not be able to pass through a Na+ channel, with some exceptions

Ion Channel Types

• There are three major types of ion channels: leak, ligand-gated, and voltage-gated

Leak Channels

• Ion channels that are always open
• These are extremely important for maintaining the membrane potential (voltage of the cell)
• Keeps the electrical environment constant during rest periods

Ligand-Gated Channels

• These are gated channels, which are closed by default
• When closed, they will not allow ions to flow in or out
• Channel has ligand binding site on the extracellular (outside) side of the protein
• Ligand is a chemical signal that binds to a binding site of a channel/receptor
• Examples: neurotransmitters, hormones, axon guidance cues, etc.
• When a ligand binds to a ligand-gated channel causing the channel to open
• The ligand acts as a key for the channel
• Each channel has its own specific ligand; so different ligands will not activate the cell, with some exceptions
• Ligand-gated channels are extremely important for the synaptic signaling in the dendrites

Voltage-Gated Channels

• Like ligand-gated channels, voltage-gated (V-gated) channels are closed in their default position
• Voltage-gated channels open when activated, but do not depend on an external ligand
• They have a specialized segment of the channel protein on the intracellular (inside) side of the neuron, which is a voltage sensor
• When the cell becomes positive enough, the voltage sensor detects it, causing the channel to open

Membrane Potentials

• All neurons are charged, due to the imbalance of positive and negative ions in the cell
• This electrical charge is called the membrane potential (aka the cell's voltage)
• The resting membrane potential (Em) is the default voltage that neurons will always return to over time
• This is maintained by leak channels
• A neuron's Em is typically negative (~ -70 mV)
• The membrane potential will change as ions flow in and out of the cell, dependent on the opening and closing of channels
• Ions cannot move across the membrane on their own
• The ions will always move down their concentration gradient, from high to low concentration
• Movement of ions will change the electrical potential (voltage) because those moving ions are charged (+ or -)

Na+ Movement

• Na+ has a very high extracellular (outside of cell) concentration and a very low intracellular (inside of cell) concentration
• When Na+ channels open, Na+ will move down its concentration gradient, flowing into the cell

Na+ Effect on Membrane Potential

• Na+ has a positive charge, so as it flows into the cell, it will cause the cell to become more positive
• The cell becoming more positive is called depolarization
• This is also called Excitatory Postsynaptic Potential (EPSP)

Depolarization

• A cell becoming more postive
• The membrane potential gets closer to 0mV
• "De" = undo, “Polar" = far away/opposite

EPSP

• Excitatory Postsynaptic Potential (EPSP) is when a cell becomes more positive
• Called "postsynaptic potential” because changes in membrane potential is typically recorded from a cell that was stimulated at synapse
• When Na+ channels open, the cell depolarizes because positive Na+ ions flow into the cell, thus causing an EPSP

EPSP - Time by Voltage Plot

• Membrane potential is often graphed on a time by voltage plot
• X-axis = time (msec) and Y-axis = voltage (mV)

EPSP Plot

• EPSPs will temporarily make the cell slightly less negative
• The cell will return to Em (~ - 70mV) because of constantly open leak channels
• This allows the cell to maintain a baseline when not stimulated

Cl- Movement

• Cl- has a greater extracellular concentration than its intracellular concentration, so Cl- will flow into the cell
• Cl- ions are negative, so the influx of Cl- will cause the cell to become more negative

Hyperpolarization

• When a cell becomes more negative
• “Hyper" = exceed/go past, “Polar” = far away/opposite
• Known as Inhibitory Postsynaptic Potential (IPSP)

IPSP Plot

• IPSPs will temporarily make the cell slightly more negative
• Membrane potential will always return to the Em (~ -70mV)

K+ Movement

• K+ is a positive ion, but the cell becomes more negative when K+ channels open

• When K+ channels open, the ions move down its concentration gradient, which is high intracellular to low extracellular

• The flux of positive ions out of the cell causes the cell to hyperpolarize (positive charges are leaving)

• Even though Na+ and K+ are both positive ions, they have inverse effects on the membrane because of concentration gradients

• Na+ = Depolarize

• K+ = Hyperpolarize

Ca2+

• Ca2+ is an exception
• Ca2+ flows down its concentration gradient as expected, but it is a weak gradient
• Very little Ca2+ flows into the cell so it does not depolarize much (when compared to other ions)
• Calcium is still the most influential ion for neurons
• It is the only ion that covered that activates proteins to do functions, such as NT release, plasticity, muscle contraction, gene expression, etc.

Excitatory Synapses

• Excitatory axons (aka axons that cause EPSPs) typically form synapses on the dendrites of cells
• EPSPs cause the dendrites to depolarize (become more positive)

EPSP Traveling

• The positive charges will not stay in the dendrites
• The positive charges will diffuse through the cell
• They travel from the dendrite, through the cell body, to the axon hillock

Action Potential Threshold

• If the axon hillock becomes positive enough, the neuron will fire an action potential (AP)
• The amount of positivity needed to fire an AP is called an AP Threshold

EPSP

• A single EPSP is a very small change in membrane potential
• EPSPs will decay slightly as it travels to the axon hillock
• A single EPSP will most likely not reach the axon hillock with enough charge to cause an AP
• This prevents neurons from being overly sensitive to spontaneous firing
• Biological systems are prone for random activity
• Neurons depend on summating multiple EPSPs to fire an AP

EPSP Summation

• There are two forms: Temporal (Time) and Spatial (Space, area)

Temporal Summation

• Two (or more) EPSPs on the same dendrite that happen in quick succession
• The EPSP will summate their depolarization and travel to the axon hillock
• The following EPSPs will add their positivity to first EPSP
• This can only happen when EPSPs are close in time; otherwise, membrane potential will return to Em if there is too much time between EPSPs

Spatial Summation

• Two (or more) EPSPs that happen at the same time at multiple dendrites
• The EPSPs from one dendrite will summate on the EPSP from another dendrite

EPSP Summation

• Temporal and spatial summation are not mutually exclusive
• Both are used to make the neuron positive enough to cause an AP
• This gives neurons the means to integrate information from very active axons and/or multiple axons

Explore the role of ion channels in neuronal signaling of neurons. Questions cover selective permeability, concentration gradients, and neurotransmitter-gated channels. Test your knowledge of voltage-gated channels, neurotoxins, and ion distribution.