Hyperpolarization

Overview:

The brain is a complex organ that performs even more complicated functions in the body than it appears to execute. However, it needs information to process and order the tissues of the body to implement the proper response, so that the body works as a whole.

To receive this information, the brain works with nerve cells and the extensive network of nerves that conduct numerous nerve impulses to and from the brain. The membrane potential developed across the nerve cell’s membrane helps in the conduction of these nerve impulses. And one of these phenomena is hyperpolarization.

Hyperpolarization is frequently triggered by a positively charged potassium K+ (a cation) outflow through K+ channels or Clˉ (an anion) inflow through Clˉ channels. 

During this period, hyperpolarization stops the nerve cell from absorbing another input or at the very least increases the barrier for any incoming stimulus. Hyperpolarization is important because it prevents any stimulus that has already been delivered up an axon from generating another action potential in the reverse direction.

In this article, the hyperpolarization phenomenon will be explained in detail, along with the importance of the process highlighted and the complications that are involved with this state of the nerve cell membrane.

Summary:

  • Hyperpolarization is a shift in the membrane potential of a cell that causes it to become more negative. It is the inverse of depolarization.
  • It suppresses action potentials by raising the stimulus necessary to push the membrane potential to the action potential barrier.
  • Hyperpolarization is frequently triggered by a positively charged potassium K+ (a cation) outflow through K+ channels or Clˉ (an anion) inflow through Clˉ channels.
  • In contrast, cation inflow, such as Na+ through Na+ channels or Ca²+ through Ca²+ channels, prevents hyperpolarization.
  • If a cell has resting Na+ or Ca²+ flux, inhibiting this current flow will also lead to hyperpolarization.
  • Following the formation of an action potential, the cell goes into a state of hyperpolarization.
  • When hyperpolarized, the nerve cell enters a refractory period lasting about 2 milliseconds, in which it would be unable to create additional action potentials. 
  • Sodium-potassium ATPases transfer positively charged potassium ions (K+) and positively charged sodium (Na+) ions till the membrane potential returns to roughly –70 millivolts, where at this stage the nerve cell can send another action potential.
  • Hypokalemia’s immediate electrophysiological actions involve resting membrane hyperpolarization, restriction of Na+-K+ ATPase, and reduction of positively charged potassium ion (K+) channel conductances, culminating in AP duration (APD) lengthening

Location:

Depolarization and hyperpolarization happen when ion channels in the membrane close or open, providing the opportunity for specific ions to access or leave the cell. Hyperpolarization can be caused, for instance, by opening channels that allow positive ions to move out of the cell (or negative ions to move in).

Hyperpolarization is a change in the membrane potential of a cell to a greater negative value (that implies that there is moving further away from zero). A hyperpolarized neuron is much less likely to induce an action potential (Figure 1).

To better understand this phenomenon, we should attempt to understand the relevance of this concept concerning nerve impulse transmission.

The membrane of nerve cells:

The nerve cell’s membrane is semi-permeable, being strongly porous to positive potassium ions and just marginally receptive to Chlorine ions and positive sodium ions.  Equilibrium between a heavy proportion of sodium ions on one side and a higher proportion of Chlorine, and also modest amounts of impermeant negative ions including such as bicarbonate, phosphate, and sulphate, on another, maintains electroneutrality in the extracellular fluid.

In the cytoplasmic region, where positive potassium ion (K+) concentrations are large, Chlorine ion concentrations are substantially lower than those required to achieve equilibrium with the sum of the positive charges. Negatively charged impermeant proteins and phosphates keep the environment electroneutral. 

When the overall concentration of ions on one end is not equivalent to that on the opposite side, water moves via the plasma membrane to preserve an osmotic equilibrium between the extracellular fluid and the cytoplasmic region. 

The three properties of the nerve cell that are: membrane semipermeability, osmotic equilibrium, and electroneutrality on both sides—create a balance of electrical potential wherein the inner region of the membrane is much more negative than the outer region.   

This potential, known as the cell membrane potential or simple membrane potential, is found in most nerve cells and ranges between sixty and seventy-five millivolts (mV; or thousandths of a volt; the minus sign depicts that the inner area is negative).

Figure 1 Hyperpolarization

The nerve cell is considered to be in a state of polarization when the interior of the cell membrane has a negative surface charge contrasted to the exterior. Any alteration in membrane potential that tends to cause the inner region to be more negative is referred to as hyperpolarization, whereas any alteration that tends to make it a little less negative is referred to as depolarization.

The Nernst potential:

The Nernst potential is the potential difference that occurs along a membrane whenever an ion has reached a steady-state between the inclination to disperse down its concentration gradient and the potential to be attracted back by the other ions, resulting in no overall flux.

The nerve cell plasma membrane is extremely porous to positively charged potassium ions (K+), and the measured membrane potential of many of these nerve cells (as described above sixty to seventy-five mV) is near to that anticipated by the Nernst equation for positive potassium ions (K+).

Nevertheless, it is not identical since positively charged potassium ions (K+) are not the only ion influencing membrane potential. In addition, the membrane is modestly porous to positively charged sodium ions (Na+) and negatively charged chloride ions (Clˉ).

Although positively charged sodium ion (Na+) penetration is poor, the large quantity of this cation just outside of the cell and the mildly negative electric charge within the cell try to push positively charged sodium ions (Na+) towards the inner side. As a result, the interior of the cell depolarizes, throwing positively charged potassium ions (K+) out of balance.

As a result, positively charged potassium ions (K+) leaks out of the cell until an equilibrium condition is established in which the leak inward of positively charged sodium ions (Na+) equals the leak outwards of positively charged potassium ions (K+) so there is no total ion flux. Because the negatively charged chloride ion (Clˉ) is at a larger concentration outside of the cell than within, it has the potential to infiltrate the membrane. As a result, for an equilibrium point to be formed, the total of all three net flows must be zero.

Through using the constant-field equation, investigators can compute the cumulative impact of positively charged potassium ions (K+), positively charged sodium ions (Na+), and negatively charged chloride ions (Clˉ) on the membrane potential provided the concentration range of all three ions per each side of the membrane and the relative permeability of the membrane to each ion.

The permeance of positively charged sodium ions (Na+), for instance, is only a small portion of that of positively charged potassium ions (K+), and the permeance of negatively charged chloride ions (Clˉ) is even lower; thus, whereas the membrane potential is very sensitive to fluctuations in positively charged potassium ion (K+) concentration, it is less sensitive to alterations in the positively charged sodium ion (Na+) amount and almost unfazed by variations in the negatively charged chloride (Clˉ) concentration.

Nerve impulse transmission in nerve cells:

When a physical input, like as feel, smell, or light, acts on a specialized sensory cell that has been particularly engineered to react to that input, the power of the stimulation (physical, chemical, or optical) is transcribed, or converted, into an electrical reaction. 

This is known as the receptor potential, a form of local potential which, when large enough in magnitude, produces a nerve impulse.  (The postsynaptic potential, or PSP, which arises in chemical sensors at the synaptic cleft, is yet another sort of local potential.)

The preceding section indicates that the electrical potential in nerve cells is dependent on the dispersion of ions all across the plasma membrane, and therefore this allocation occurs via membrane penetration. In addition, ions are usually always hydrated in the shape of ion-water combinations, which have a tough time crossing the plasma membrane’s hydrophobic (water-hating) lipid bilayer.

Permeation happens via membrane proteins anchored in the lipid bilayer and traversing the barrier from the cytoplasmic region to the extracellular fluid.

Such components regulate the electrical dispersion that maintains the membrane polarised by pushing ions from one end to another and by actually giving pathways via which dispersing ions can move past the lipid molecules, they both sustain the ionic dispersion that retains the membrane polarized and enable for abrupt shifts in dispersion that generate nerve impulses.

An action potential is an electrical signal that goes within nerve cells and enables nerve cells to communicate by generating neurotransmitter secretion. Neurotransmitter is a chemical molecule produced by a nerve cell that is used to interact with another nerve cell. 

The electrical charge mismatch that occurs between the inside of electrically excitable nerve cells (also called neurons) and their environment is known as resting potential. Electrically trigger-able cells have a resting potential in the spectrum of sixty to ninety-five millivolts (where 1 millivolt is equal to 0.001 volts), with the inner side of the cell negatively electrified.

The cell or membrane is considered to be hyperpolarized if everything inside the cell becomes much more electronegative (— for example, the potential tends to get higher than the resting potential). Depolarization occurs when the interior of the cell will be less negative (— for example, the potential falls below the resting potential).

The action potential is the transient depolarization that happens during nerve conduction when inside the neuron fibre gets positively charged. This relatively short change in polarization is thought to be caused by the movement of positively charged sodium ions externally to the inner side of the cell, consequences in nerve impulse transfer.

Following depolarization, the cell membrane gets highly porous to potassium ions that have a positive charge on them, which flow in an outward direction from the cell’s interior region, where they ordinarily present in quite high concentrations. The cell then returns to the negatively charged state that distinguishes the resting potential.

During the refractory period, which occurs after hyperpolarization but before the nerve cell returns to its resting potential, the nerve cell can trigger an action potential thanks to the capacity of the sodium channels to open; that being said, because the nerve cell is much more negative, reaching the action potential threshold will become more challenging.

Figure 2 Action Potential

There is another kind of potential, known as the postsynaptic potential, or the PSP. Postsynaptic potential (PSP), a brief shift in the electric polarization of a nerve cell’s membrane (neuron). The postsynaptic potential is the outcome of the chemical transfer of a nerve impulse at the neuronal junction (also called a synapse), and it can result in the triggering of a further impulse.

When a signal from an active nerve cell (in this case, a presynaptic neuron) lands at a synapse, a chemical compound called a neurotransmitter is produced, forcing molecular structures that are in the shape of channels in the membrane of the resting nerve cell to open (postsynaptic nerve cell). Ions moving through the pathways cause a change in the resting membrane polarization, which is normally more negative within the membrane.

It is now clear that the ions pouring through the outlets cause a change in the resting membrane polarization, and that is probably somewhat more negative within the nerve cell than on the outer side of it. 

Hyperpolarization, as you know by now is defined as a rise in negative charge on the interior of the nerve cell, is an inhibiting Postsynaptic potential (also shortly referred to as the PSP) because it prevents the nerve cell from generating an impulse.

Depolarization, or a reduction in negative charge, is an activating Postsynaptic potential (or shortly known as the PSP) as it can promote the formation of a nerve impulse if the nerve cell exceeds the essential threshold potential (action potential).

The Postsynaptic potential (or the PSP) is a graded potential, which means that its level of hyperpolarization or depolarization fluctuates with ion channel stimulation. The capacity of nerve cells to incorporate several polysynaptic potentials (or PSPs) at numerous synapses is referred to as summation. Summation could be either spatial (signals are acquired from multiple synapses in one go) or temporal (signals are obtained sequentially).

As mentioned before that summation can be either spatial (messages are acquired from multiple synapses at the same time) or temporal (signals are collected from the very same synapse at different times). It is also important to note that both of these kinds of summations, Spatial and temporal summations, can happen at the same time.

The end-plate potential is the analog of the polysynaptic potential (or the PSP) at nerve-muscle synapses. 

Complications involving hyperpolarization:

Hypokalemia:

Hypokalemia is most typically seen in medicine as a side effect of diuretic therapy, which can be used to treat hypertension, heart problems, kidney illness, as well as other disorders. Its immediate electrophysiological actions involve resting membrane hyperpolarization, restriction of Na+-K+ ATPase, and reduction of positively charged potassium ion (K+) channel conductances, culminating in AP duration (APD) lengthening, decreased repolarization reserve, and EAD, DADs, and automaticity.

Hyperkalemia can be either systemic or interstitial (limited to heart or other tissue as a consequence of acute global or regional ischemia). These conditions increase the likelihood of arrhythmia.

Hypokalemia has traditionally been ascribed to an immediate reduction of positively charged potassium ions (K+) channel conductances, but new research suggests that indirect impacts of hypokalemia lead to the activation of late Na+ and Ca²+ streams also play a significant role. 

These two mechanisms work together to reduce repolarization capacity considerably to elicit EADs and EAD-mediated arrhythmias such as TdP, polymorphic VT, and VF.

Polymorphic ventricular tachycardia (PVT) is a type of ventricular tachycardia where there are several ventricular foci with varied amplitude, axis, and length of the QRS complex. Myocardial ischaemia/infarction is by far the most frequent source of PVT.

Torsades de pointes (TdP) is a type of PVT that occurs during QT prolongation; it has a distinct shape in which the QRS complexes “coil” around the isoelectric line. 

Conclusion:

Hyperpolarization is a change in the membrane potential of a cell to a greater negative value (that implies that there is moving further away from zero). A hyperpolarized neuron is much less likely to induce an action potential. The action potential is the transient depolarization that happens during nerve conduction when inside the neuron fibre gets positively charged. This relatively short change in polarization is thought to be caused by the movement of positively charged sodium ions externally to the inner side of the cell, consequences in nerve impulse transfer. Hypokalemia’s immediate electrophysiological actions involve resting membrane hyperpolarization, restriction of Na+-K+ ATPase, and reduction of positively charged potassium ion (K+) channel conductances.  

Reference list

  • Encyclopedia Britannica (2021a) nervous system – The neuronal membrane, 15 August. Available at: https://www.britannica.com/science/nervous-system/The-neuronal-membrane#ref606370 (Accessed: 15 August 2021).
  • Encyclopedia Britannica (2021b) Postsynaptic potential | biology, 15 August. Available at: https://www.britannica.com/science/postsynaptic-potential (Accessed: 15 August 2021).
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399982/