Membrane potential and action potential

Neuron signalling

What forces move ions across membranes?

Chemical force and electrical force

Chemical force

Differences in concentrations - diffusion from a region of high concentration to a region of low concentration.

Electrical force

Interior cell is negatively charged so positively charged cations are retained and negative ions will be expelled.

Electrochemical force

A driving force which is a combination of the chemical and electrical forces acting on any particular ion.

Movement of ions across cell membranes - the 2 broad categories of ion channels

Channels that are always open.

Channels that are gated.

They facilitate ion movements into and out of neurons.

Movement of ions across cell membranes - gated channels

They require a stimulus to open - ligands, mechanical force or voltage, specific to particular ions.

Movement of ions across cell membranes - open channels

They allow free movement of ions.

Chemical gradient across the neuronal membrane - under resting conditions

The concentration of Na+ ions is 10x higher outside the neuron compared to inside it.

At the same time, levels of K+ ions are 15x higher inside the neuron compared to the extracellular environment.

Potassium movement

There is a constant flow of K+ ions down their concentration gradient, from the inside of the neuron to the outside.

This movement occurs via open (or leaky) K+ channels that are situated in the membrane of the neuron.

Na+/K+ ATPase pump

The ion gradient is maintained by the continuous operation of the Na+/K+ ATPase pump.

It moves 3Na+ ions from the inside of the neuron to the outside of the cell.

At the same time, 2 K+ ions are moved from outside the neuron to the inside of the cell.

At each cycle of the Na+/K+ ATPase pump, the cell loses one positively charged ion from the intracellular environment.

How the resting membrane potential

The ultimate result between the diffusion of K+ and the action of the Na+/K+ ATPase pump is a more positively charge outside the neuron compared to the inside of the neuron.

At rest, there is more positively charge outside the neuron compared to the inside of the neuron.

Polarisation

The difference in charge across the membrane of the neuron.

Resting membrane potential

The difference in voltage across the plasma membrane when the neuron is at rest. For most neurons it is -70mV.

Forces that drive ion movement

When ion channels open, the chemical gradient drives ion movement from high concentration to low concentration. In the absence of polarisation, diffusion would occur until chemical equilibrium was reached. However, this does not occur because of electrical forces.

Electrochemical gradients of sodium - when Na+ channels open...

chemical gradient drives ion movement into the cell, electrical force pulls + ions into the cell and both act in the same direction + Na+ will enter the cell.

Equilibrium of sodium movement

As Na+ moves into the neuron, the charge inside the cell starts to become positive and the electrical gradient decreases, along with the chemical gradient. Eventually, the chemical and electrical forces will be exactly in balance and there will be no net flow through any open channels.

Equilibrium potential

The membrane potential required to exactly counteract the chemical forces acting to move one particular ion across the membrane.

Electrochemical gradient of potassium - when K+ channels open...

chemical gradient drives ion movement out of the cell but electrical force pulls + ions into the cell. Two forces act in opposite directions. Chemical force > electrical force, so K+ moves out of the neuron.

Equilibrium of potassium movement

As K+ moves out of the neuron, the charge inside the cell starts to become even more negative, so the electrical gradient becomes stronger. Eventually, the chemical force that drives K+ out of the cell = the electrical force driving K+ back into the cell. At this point, there will be no net flow of K+ ions.

The equilibrium potential (E) can be calculated using...

the Nernst equation.

The Nernst equation

E = 61/z log (Co/Ci)

E - equilibrium potential in millivolts (mV)

z = charge (valence) of the ion

Co = concentration of the ion outside the neuron

Ci = concentration of the ion inside the neuron

Voltage-gated ion channels

Embedded in the plasma membrane of the neuron are ion channels that are sensitive to the voltage of the cell. These channels open only when the voltage in the cell reaches a certain value.

Voltage-gated Na+ channels - gates at rest

Voltage-gated Na+ channels have both an activation gate and an inactivation gate. At rest, the activation gate is closed and the inactivation gate is open.

Voltage-gated K+ channels - gates at rest

Voltage-gated K+ channels have one activation gate, which opens to allow the flow of K+ ions through the channel and closes to stop the flow of K+ ions.

Neuron at rest

When the membrane potential is -70mV, voltage-gated Na+ channels are closed and the concentration of Na+ outside the cell is higher than inside the cell.

Initial stimulation

When the neuron receives an excitatory signal or stimulus, ligand-gated ion Na+ channels open. Small amounts of Na+ will move down their concentration gradient into the neuron and the resting potential will start to become more positive.

Steps of stimulations of neurons

Initial stimulation

Depolarisation

Inactivation of Na+ channels

Repolarisation

Hyperpolarisation

Refractory period

Depolarisation

Once the membrane potential reaches a critical threshold of -55mV, voltage-gated activation gates in the Na+ channel open quickly, allowing Na+ to flood into the neuron. As a result of the large influx of positively charged Na+, the neuron quickly loses its negative charge and undergoes depolarisation.

Inactivation of Na+ channels

When the inside of the neuron become highly positive, the pore of the voltage-gated Na+ channels is plugged by the inactivation gate and the flow of Na+ into the neuron stops.

Repolarisation

Eventually the intracellular environment of the neuron becomes sufficiently positive that voltage-gated K+ channels begin to open slowly. Opening of these channels allows K+ to flow down its concentration gradient out of the cell. This movement of K+ causes the inside of the neuron to quickly regain its negative charge in a process called repolarisation.

Hyperpolarisation

In response to the increasingly negative charge inside the neuron, the voltage-gated K+ channels close. Because this process is slow, some K+ ions continue to move outside the cell while the channel is closing. This extra efflux of K+ causes the membrane potential to become more negative than the resting potential of -70mV. This process is called hyperpolarisation.

Refractory period

During the period of hyperpolarisation, the neuron will not be able to fire another action potential. This is termed the refractory period. Eventually, the action of the Na+/K+ ATPase pump will restore the resting membrane potential to -70mV and the neuron will be ready to fire another action potential.