Hyperpolarization

The Hyperpolarization is a biological process in which the membrane tension increases and exceeds the resting value. This mechanism is important for the function of muscle, nerve and sensory cells in the human body. It enables actions such as muscle movements or vision to be enabled and controlled by the body.

What is the hyperpolarization?

Cells in the human body are enclosed by a membrane. It is also known as the plasma membrane and consists of a lipid bilayer. It separates the intracellular area, the cytoplasm, from the surrounding area.

The membrane tension of cells in the human body, such as muscle, nerve or sensory cells in the eye, have a resting potential when at rest. This membrane tension arises from the fact that there is a negative charge inside the cell and in the extracellular area, i.e. outside the cells, there is a positive charge.

The value for the resting potential differs depending on the cell type. If this resting potential of the membrane voltage is exceeded, hyperpolarization of the membrane occurs. This makes the membrane voltage more negative than during the rest potential, i.e. the charge inside the cell becomes even more negative.

This usually takes place after the opening or also closing of ion channels in the membrane. These ion channels are potassium, calcium, chloride and sodium channels that function in a voltage-dependent manner.

The hyperpolarization occurs due to voltage-dependent potassium channels, which need a certain time to close after the resting potential is exceeded. They transport the positively charged potassium ions into the extracellular area. This briefly leads to a more negative charge inside the cell, the hyperpolarization.

Function & task

The hyperpolarization of the cell membrane is part of the so-called action potential. This consists of different stages. The first stage is the exceeding of the threshold potential of the cell membrane, followed by depolarization, there is a more positive charge inside the cell. This then leads to repolarization, which means that the resting potential is reached again. Then the hyperpolarization takes place before the cell reaches the resting potential again.

This process is used to relay signals. Nerve cells form action potentials in the area of ​​the axon mound after they have received a signal. This is then passed on in the form of action potentials along the axon.

The synapses of the nerve cells then transmit the signal to the next nerve cell in the form of neurotransmitters. These can have an activating effect or also have an inhibiting effect. The process is essential in the transmission of signals, for example in the brain.

Seeing is done in a similar way. Cells in the eye, the so-called rods and cones, receive the signal from the external light stimulus. This leads to the formation of the action potential and the stimulus is passed on to the brain. Interestingly, the stimulus development does not take place here as with other nerve cells through depolarization.

In their resting position, nerve cells have a membrane potential of -65mV, whereas visual cells have a membrane potential of -40mV at a resting potential. This means that they already have a more positive membrane potential than nerve cells when they are at rest. In the case of visual cells, the stimulus is developed through hyperpolarization. As a result, the visual cells release fewer neurotransmitters and the downstream nerve cells can determine the intensity of the light signal based on the reduction in neurotransmitters. This signal is then processed and evaluated in the brain.

The hyperpolarization triggers an inhibitory postsynaptic potential (IPSP) in the case of vision or in certain neurons. In contrast, neurons are often activating postsynaptic potentials (APSP).

Another important function of hyperpolarization is that it prevents the cell from re-triggering an action potential too quickly based on other signals. So it temporarily inhibits the generation of stimuli in the nerve cell.

Illnesses & ailments

Heart and muscle cells have HCN channels. HCN stands for hyperpolarization-activated cyclic nucleotide-gated cation channels. These are cation channels that are regulated by the hyperpolarization of the cell. 4 forms of these HCN channels are known in humans. They are referred to as HCN-1 through HCN-4. They are involved in the regulation of the heart rhythm and in the activity of spontaneously activating nerve cells. In neurons they counteract hyperpolarization so that the cell can reach the resting potential more quickly. So they shorten the so-called refractory period, which describes the phase after depolarization. In cardiac cells, however, they regulate the diastolic depolarization, which is generated at the sinus node of the heart.

In studies with mice, the loss of HCN-1 has been shown to create a motor movement defect. The absence of HCN-2 leads to neuronal and cardiac damage and the loss of HCN-4 leads to death of the animals. It has been speculated that these channels may be linked to epilepsy in humans.

In addition, mutations in the HCN-4 form are known that lead to cardiac arrhythmia in humans. This means that certain mutations of the HCN-4 channel can lead to a disturbance of the heart rhythm.The HCN channels are therefore also the target of medical therapies for cardiac arrhythmias, but also for neurological defects in which the hyperpolarization of the neurons lasts too long.

Patients with cardiac arrhythmias that can be traced back to a malfunction of the HCN-4 channel are treated with specific inhibitors. However, it must be mentioned that most therapies relating to the HCN channels are still in the experimental stage and are therefore not yet accessible to humans.