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Leak channels

Introduction to the structure and function of the cell membrane of a neuron and its involvement in facilitating electrochemical events necessary for neuronal function.

Leak channels, also referred to as leakage or passive channels, represent the most basic type of ion channel found in cells, essential for shaping the membrane's potential difference. Unlike other ion channels, leak channels are non-gated and remain continuously open, regardless of external stimuli. This perpetual openness enables ions to move across the membrane according to their respective electrochemical gradients, ensuring a steady flow of ions.

Key facts about the leak channels
Definition Leak channels are non-gated ion channels of the cell membrane that remain constantly open. They are highly selective, allowing specific ions to pass through them
Types of leak channels The main types of leak channels in the human CNS:
Potassium leak (K+) channels
Sodium leak (Na+) channels
Chloride leak (Cl-) channels
Electrochemical gradient The ions pass through leak channels following the
- chemical gradient, which makes ions move from higher to lower concentration, and the
- electric gradient, which makes ions move toward the opposite electric charge
Potentials depending on the function of leak channels Equilibrium potential
The potential at which chemical and electrical gradient of a specific ion are in balance

Resting potential

The potential of the cell’s membrane when at rest
Contents
  1. Main types of leak channels on neurons
  2. The electrochemical gradient
  3. The equilibrium potential of ions
    1. Cells with one type of leak channels
    2. Cells with two or more types of leak channels
  4. Leak channels, Na+/K+ pump, and ion transporters shape the neuronal resting potential
  5. Sources
+ Show all

Main types of leak channels on neurons

Leak channels are not gated and are constantly open, but they are highly specific, with each one allowing only a particular type of ion to pass through. The following types of leak channels have been found in the human central nervous system (CNS):

  • Potassium leak (K+) channels
  • Sodium leak (Na+) channels
  • Chloride leak (Cl-) channels

The electrochemical gradient

Different cells in the human nervous system exhibit varying distributions of leak channels on their membrane. For instance, in most glial cells, the overwhelming majority is K+ leak channels. In contrast, neurons contain a significant number of both K+ and Na+ leak channels, while Cl- channels are found in specific types of neurons. Each of these cells maintains a specific potential difference. Every time a graded potential or an action potential depolarizes or hyperpolarizes part of a neuron's membrane, the leak channels serve as a pathway for ions to return and repolarize the membrane.

When in the resting state, the extracellular fluid contains a higher concentration of Na+ and Cl-, while the cytoplasm has higher concentration for K+ and organic anions, such as proteins and amino acids. Ions can pass through the leak channels following their electrochemical gradient. The electrochemical gradient results from two gradients: the chemical gradient, which makes ions move from higher to lower concentration, and the electric gradient, which makes ions move toward the opposite electric charge.

The equilibrium potential of ions

To understand the dynamic balance between electrical and chemical gradients acting on ions, let's first consider what happens when a cell has only one type of leak channel. Then, we will explore the situation with two or more types of leak channels.

Cells with one type of leak channels

In the case of cells with one type of leak channels, like glial cells with K+ leak channels, when a part of the membrane is depolarized the course of K+ ions is as follows:

  1. Initially, K+ ions, following their chemical concentration gradient, move to the lower concentration outside the cell.
  2. The positively charged K+ ions gradually make the extracellular side of the membrane more positive, while the electric charge of the intracellular side becomes increasingly negative. Consequently, the potential difference starts returning to the previous, more negative state.
  3. At a certain point, when the extracellular fluid becomes positive enough and the cytoplasm becomes negative enough, the electrical gradient pushes the ions in the opposite direction of the chemical gradient, into the cell. Thus, there are two opposing gradients acting on the K+ ions.
  4. Eventually, a dynamic balance is reached where, for each K+ ion moving out of the cell, another K+ ion passes into the cell. At this equilibrium point, the potential difference reaches a stable level called the “equilibrium potential of K+ ions (EK)”.

Cells with two or more types of leak channels

Unlike glial cells, most neurons in the CNS have both K+ and Na+ leak channels which contribute to the resting potential regulation:

  1. Both chemical and electrical gradients drive Na+ ions into the cytoplasm, with an equilibrium potential for Na+ (ENa) +55 mV.
  2. For K+ ions chemical and electrical gradients are opposite and finally move ions out of the cell into the extracellular fluid, with an equilibrium potential for K+ (EK) which is -75 mV.
  3. The resulting dynamic balance depends on both the movements of K+ and Na+. The neuron’s resting potential, influenced by the leak ion channels, exhibits two key properties:
  • It falls between EK and ENa.
  • It tends to align more closely with the equilibrium potential of the ion for which the membrane has a higher permeability, typically determined by the number of leak ion channels. Since neurons usually have more K+ leak channels than Na+ channels, the resting potential is closer to EK than to ENa.

The same principle applies when three ions (K+, Na+, and Cl-) are involved, and the resting potential falls between the equilibrium potentials of the three ions. Organic anions do not participate in this process, as they are unable to pass through the cell membrane. Their presence helps maintain a constant negative charge inside the cell but does not directly influence the resting potential.

Leak channels, Na+/K+ pump, and ion transporters shape the neuronal resting potential

In a real neuron, the resting membrane potential is maintained primarily by passive ion flow through leak channels, with the active transport of ions by the Na+/K+ pump helping to restore ion gradients. Here's how these mechanisms work together:

  1. Leak Channels: Na+ ions passively diffuse into the neuron, and K+ ions diffuse out of the neuron through their respective leak channels. This passive movement of ions through the membrane would gradually disrupt the electrochemical gradients, shifting the membrane potential away from its resting value.
  2. Na+/K+ Pump: To counterbalance the passive ion flow, the Na+/K+ pump actively transports 3 Na+ ions out of the cell and 2 K+ ions into the cell, using ATP. This active transport works against the electrochemical gradients, helping to maintain the proper intracellular concentrations of Na+ and K+. While the pump operates more slowly than ion channels, its function is essential for resetting and preserving the resting membrane potential after fluctuations due to ion movement.
  3. Cl- Transport: Unlike Na+ and K+, Cl- ions are primarily regulated by cotransporters like the Na+/K+/Cl- cotransporter and the K+/Cl- cotransporter. These cotransporters use the energy from the movement of Na+ and K+ to maintain Cl- balance by either moving Cl- into or out of the cell, depending on the needs of the neuron. The Cl- balance contributes to stabilizing the membrane potential but does not involve direct ATP consumption like the Na+/K+ pump.

Together, these mechanisms — passive ion movement through leak channels, active transport by the Na+/K+ pump, and cotransporters for ions like Cl- — ensure that the neuron maintains a stable resting membrane potential. This dynamic equilibrium prevents the cell from drifting too far from its resting potential and ensures the neuron is ready to respond to signals.

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