Hyperpolarization is a biological process in which the membrane voltage increases and exceeds the resting value. This mechanism is important for the function of muscle, nerve as well as sensory cells in the human body. Through it, actions such as muscle movement or vision can be enabled and controlled by the body.
What is hyperpolarization?
Hyperpolarization is a biological process in which the membrane voltage increases and exceeds the resting value. This mechanism is important for the function of muscle, nerve as well as sensory cells in the human body. Cells in the human body are enclosed by a membrane. It is also called 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 cells, nerve cells, or sensory cells in the eye, have a resting potential in the resting state. This membrane voltage is caused by the fact that there is a negative charge inside the cell and a positive charge in the extracellular area, i.e. outside the cells. The value for the resting potential varies depending on the cell type. If this resting potential of membrane voltage is exceeded, membrane hyperpolarization occurs. As a result, membrane voltage becomes more negative than during the resting potential, i.e. the charge inside the cell becomes even more negative. This usually occurs after the opening or even closing of ion channels in the membrane. These ion channels are potassium, calcium, chloride , and sodium channels, which function in a voltage-dependent manner. Hyperpolarization occurs due to voltage-dependent potassium channels that take time to close after the resting potential is exceeded. They transport the positively charged potassium ions into the extracellular region. This briefly results in a more negative charge inside the cell, hyperpolarization.
Function and task
The hyperpolarization of the cell membrane is part of the so-called action potential. This consists of several stages. The first stage is the crossing of the threshold potential of the cell membrane, followed by depolarization, there is a more positive charge inside the cell. This is followed by repolarization, which means that the resting potential is reached again. This is followed by hyperpolarization before the cell reaches the resting potential again. This process serves to transmit signals. Nerve cells form action potentials in the axon hillock region after receiving a signal. This is then transmitted along the axon in the form of the action potentials. 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 an inhibitory effect. The process is essential in the transmission of signals in the brain, for example. Vision also occurs in a similar way. Cells in the eye, the so-called rods and cones, receive the signal from the external light stimulus. This results in the formation of the action potential and the stimulus is then transmitted to the brain. Interestingly, here the stimulus development does not occur by depolarization as in other nerve cells. Nerve cells have a membrane potential of -65mV in their resting position, whereas photoreceptors have a membrane potential of -40mV at a resting potential. Thus, they already have a more positive membrane potential than nerve cells in their resting state. In photoreceptor cells, the development of the stimulus occurs through hyperpolarization. As a result, the photoreceptors release less neurotransmitter and the downstream neurons can determine the intensity of the light signal based on the reduction in neurotransmitter. This signal is then processed and evaluated in the brain. Hyperpolarization triggers an inhibitory postsynaptic potential (IPSP) in the case of vision or certain neurons. In the case of neurons, on the other hand, it is often activating postsynaptic potentials
(APSP). Another important function of hyperpolarization is that it prevents the cell from re-triggering an action potential too quickly due to other signals. Thus, it temporarily inhibits stimulus formation in the nerve cell.
Diseases and disorders
Heart and muscle cells have HCN channels. HCN here stands for hyperpolarization-activated cyclic nucleotide-gated cation channels.They are cation channels regulated by the hyperpolarization of the cell. In humans, 4 forms of these HCN channels are known. They are referred to as HCN-1 through HCN-4. They are involved in the regulation of cardiac rhythm as well as in the activity of spontaneously activating neurons. In neurons, they counteract hyperpolarization so that the cell can reach the resting pontential more quickly. They thus shorten the so-called refractory period, which describes the phase after depolarization. In heart cells, on the other hand, they regulate diastolic depolarization, which is generated at the sinus node of the heart. In studies with mice, loss of HCN-1 has been shown to produce a defect in motor movements. The absence of HCN-2 leads to neuronal and cardiac damage, and the loss of HCN-4 causes death in the animals. It is speculated that these channels may be associated with epilepsy in humans. In addition, mutations in the HCN-4 form are known to cause cardiac arrhythmia in humans. This means that certain mutations of the HCN-4 channel can lead to cardiac arrhythmia. Therefore, HCN channels are also the target of medical therapies for cardiac arrhythmias, but also for neurological defects in which hyperpolarization of neurons lasts too long. Patients with cardiac arrhythmias due to HCN-4 channel dysfunction are treated with specific inhibitors. However, it must be mentioned that most therapies concerning HCN channels are still in the experimental stage and therefore not yet accessible to humans.
