Membrane Potential: Depolarization and Hyperpolarization
In an animal’s nervous system, brain cells called neurons are unique in the fact that they transmit electrical signals or action potential down their axons. It is this action potential that brings the sensory information from the body to the brain. The word depolarization means in physiological terms any reduction in the voltage difference across the cell membrane, which can mean a graded potential as well as an action potential. Hyperpolarization or repolarization is the opposite of depolarization, meaning the increase in the voltage difference across the cell membrane, which results in “preventing” depolarization. In relation to an action potential, depolarization is the first phase, or rising phase, of an action potential, while hyperpolarization is the last phase, or falling phase, of an action potential. In general, depolarization and action potentials occur in unidirectional motor neurons, meaning that the action potential travels away from the neuron’s cell body and down its axon. An action potential is a short-lasting electrical impulse on the plasma membrane of cells.
Resting Membrane Potential
A neuron has fingerlike projections surrounding the soma known as dendrites as well as a single axon. The dendrites capture the electrical or chemical signals being sent from other neurons. If the signal is large enough, the dendrite will conduct the impulse to other parts of the cell. More specifically, the signal is transferred from the dendrites to the soma. Once it reaches the soma, the signal continues to an area known as the axon hillock. If the signal is large enough to elicit an action potential, it will conduct this electrical potential down the axon and finally to the axon’s terminal branches.
When neurons are at rest they present an uneven distribution of ions across the plasma membrane. This means that the inside of a neuron is more negatively charged than the outside of a neuron. This phenomenon is known as resting membrane potential, which is essentially the voltage difference between the inside and outside of a cell. The main ions that create this uneven distribution of charges across the plasma membrane are sodium (Na+), which has a significantly higher concentration (both chemically and electrically) outside the cell, and potassium (K+), which is significantly more abundant inside the cell. Even though both of these are cations, the degree of positivity is greater outside the cell compared to the inside, with the inside of the cell having a net charge that is negative. Thus, a charge difference or electric gradient is created across the cell’s plasma membrane. It is important to note that the majority of a neuron’s cytoplasm and the extracellular fluid that surrounds the outside of the neuron are electrically neutral. The charge difference only occurs across the cell membrane where the cations line the plasma membrane on both sides.
One way of modifying the distribution of ionic charges is through facilitated diffusion. Facilitated diffusion is the process of allowing the ions to flow from areas of high concentration gradients to areas of low concentration gradients. There are specific channels or pumps that allow this to occur. Many different types of channels exist that allow this exchange to happen, but most are Na+, K+, and/or chloride (Cl−) channels. The channels are made of specific proteins that are bound to the plasma membrane. The first type of ion channel is known as a leakage channel. These channels are always open, allowing ions to freely flow into and out of the neuron; however, they do conduct the flow of ions in one direction if a certain voltage difference is reached across the membrane.
A second type of ion channel, which is not always open, is known as a gated channel. A ligand-gated channel is a type of channel that opens upon chemical stimulation. These channels bind to specific types of neurotransmitters (natural and/or manmade chemicals) in order for them to open. Once they open, because there is a greater distribution of Na+ outside the cell, diffusion will occur down the electrochemical gradient, creating an inflow of Na+ inside the cell. While this is happening, there is also an outflow of K+ outside the cell. The result of this chemical transfer causes a local depolarization of the plasma membrane, known as a graded potential.
Depolarization occurs when there is more positive charge inside the cell than outside. The greater the stimulus, specifically what is received at the dendrites, the greater the depolarization will spread throughout a given neuron. Therefore the more neurotransmitter that is dumped onto the ligand-gated channels, the more channels will open. In turn, increased amounts of Na+ will flow into the cell, resulting in a greater depolarization. The depolarization of a cell membrane decays with distance from the stimulus. This means that the depolarization will be much greater around the dendrites and the soma of a neuron versus the axon terminal branches.
If a stimulus is strong enough, it will depolarize a neuron all the way to the axon hillock. The majority of neurons at rest usually have a voltage of −70 mV. They depolarize when Na+ flows inward and changes the voltage inside the cell to be more positive. When a neuron’s membrane potential is depolarized by a 15 mV threshold, which is −55 mV for a resting membrane potential of −70 mV, the production of an action potential will occur. This is because action potentials follow the “all-or-none” law, which is defined by a neuron responding to a stimulus completely or not at all. For most neurons, the membrane potential must reach a threshold between −60 mV and −45 mV to overcome this all-or-none phenomenon.
Once the local current reaches the axon hillock and the membrane potential is at or above the threshold, voltage-gated channels along the axon open. These channels will allow more Na+ to enter the cell’s axon at their location, which allows the action potential to be elicited and conducted. These specialized proteins are called voltage-gated channels because the −55 mV threshold generates enough voltage to open the channels.
There are two main types of voltage-gated channels: fast-opening Na+ channels and slow-opening K+ channels. The first ones to open are the Na+ voltage-gated channels, allowing all the Na+ present on the outside of the cell to flow into the axon through normal diffusion. This causes the neuron to be depolarized at the axon level. The more Na+ that enters the axon hillock, the more adjacent Na+ voltage-gated channels open up, creating a positive feedback loop. This phenomenon progresses throughout the entire length of the axon, causing the inside of the cell to change from −55 mV to +30 mV almost instantaneously. This radical shift of opening Na+ channels shows how the neuron’s membrane changes its permeability so that Na+ can rush down its electrochemical gradient and quickly depolarize a cell.
Once the voltage reaches between +30 mV and +50 mV, the depolarization phase of an action potential hits its peak. Immediately, the voltage-gated Na+ channels close and the voltage-gated K+ channels open. This is the beginning of the hyperpolarization phase or the falling phase of an action potential, which brings the membrane potential back toward the cell’s resting membrane potential. Repolarization occurs when the voltage-gated K+ channels open, causing K+ to flow down its electrochemical gradient and exit the cell. Again, this radical shift of closing Na+ channels and opening K+ channels shows how the neuron’s membrane changes its permeability quickly so that K+ ions can rush out of the cell.
During the falling phase, Cl− channels also open and allow these anions to enter the cell. This makes the membrane potential to become even more negative. Since the K+ channels are slow at opening and closing, the membrane potential will go past (or undershoot) the resting potential. This makes the neuron hyperpolarized as well as making it more difficult for another action potential to occur. This more negative membrane potential is called the refractory period, which makes the neuron physiologically unable to generate another action potential until this period is over. Eventually, through the leakage channels and pumps, the neuron’s membrane voltage returns to its resting membrane potential of −70 mV. This process occurs over and over again and is the primary way neurons and their target cells communication with each other.
Michael Romani and Jennifer L. Hellier
See also: Action Potential; Axon; Sensory Receptors
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