The Different Types of Membrane Channels and Pumps

By Avalon Marker and Shelby Pickett

Shelby Pickett

Avalon Marker

Channels and Pumps

Overview of Channels

• Membrane Permeability

• The ease with which molecules pass through the membrane barrier.

• The cell membrane is selectively permeable and only allows specific molecules to enter the cell.

• The permeability of the membrane is the rate of passive diffusion of molecules across the membrane.

• (Insert image of the permeability of the different molecules)

• Resting Neuronal membrane

• Ion channels:

• • • Ion channels are integral membrane proteins composed of several subunits. The primary function of ion channels in neurons is to generate transient electoral signals.

• Categories of Channels:

• • • Leakage (include a link to the chapter on resting membrane potential)
      • Leakage gated channels always remain open for substances and ions. They have constant permeability.

• Gated Channels: open in response to specific changes in membrane potential of the channel.

• Mechanically Gated

• Voltage Gated: these channels open and close in response to specific changes in membrane potential.

• Ligand gated:

• • • • • A ligand is…
        • When the ligand binds it opens the channel.

• Signal Gated

• Transporters: a membrane protein involved in the movement of ions, small molecules, and macromolecules (such as proteins) across a membrane.

• • • • They may help with transport through facilitated diffusion, active transport, osmosis, or reverse diffusion.

• Pumps

Leakage Channels

• Na+ and K+ channels.

• • K2P Gene: these are 2-pore domain potassium channels (K2P) that are responsible for the background, leakage currents that stabilize the resting membrane potential and regulate neuronal excitability.
  • NALCN  = the gene for Na+ leakage.

Voltage Gated Channels

• Na+
• K+
• Ca2+ = Transmitter release.
  • Found on the presynaptic axon terminal
  • Voltage-gated calcium channels (CaVs) are transmembrane proteins activated by depolarization of membrane potential. The calcium that enters through CaVs is crucial for cellular processes including gene expression, hormone release, neurotransmitter release, cardiac muscle contraction, and pacemaker activity.
  • Based on their activation threshold, CaVs are classified as either high or low voltage activated (HVA and LVA).
  • Genes that encode for voltage-gated calcium channels are grouped into three subfamilies, each with their own distinct function:
    • The CaV1 subfamily conducts L-type Ca currents
      • CACNA1S, CACNA1C, CACNA1D, and CACNA1F
    • The CaV2 subfamily conducts N-, P/Q-, and R-type Ca currents
      • CACNA1A, CACNA1B, and CACNA1E
    • The CaV3 subfamily conducts T-type Ca currents
      • CACNA1G, CACNA1H, and CACNA1I
  • L, N, T type currents
    • L-type Ca currents (High-threshold calcium current ICa(L)) initiate excitation-extraction coupling in muscle cells and secretion in endocrine cells, control gene transcription, as well as controlling many enzymes.
    • N-, P/Q-, and R-type Ca currents (ICa(P), ICa(Q), ICa(N), ICa(R)) and the associated CaV2 subfamily are often found concentrated in nerve terminals where Ca influx is required for the release of chemical neurotransmitters; P/Q- and R-types currents are poorly understood.
    • T-type Ca currents (ICa(T)) are activated at negative membrane potentials and are transient; these are modulated by muscarinic acetylcholine receptors. These particular channels are important as they are seen in cells that repetitively fire, such as sinoatrial nodal cells that serve as pacemakers in the heart or neurons in the thalamus that generate sleep rhythms.
    • Synaptic transmission is triggered by opening of mainly N- and P/Q-type calcium channels
  • Pore is formed by the α1 subunit
    • This is similar to the voltage-gated Na+ channel α subunit
    • α2 and δ subunits are associated glycoproteins
    • β subunits are intracellular

Ligand Gated Channels

• Ionotropic receptors.
• Ligand-gated Calcium Channels
  • There are no ligand-gated channels specifically for Ca, though nicotinic ACh receptors, 5-HT3 receptors, and all types of glutamate receptors are known as non-selective cation channels, which allow flow of Na, K, Ca, and other cations. While ACh and 5-HT3 receptors allow mostly Na & K to pass, glutamate receptors allow a significant amount of Ca to pass through.

Signal Gated Channels

• Muscarinic AcH receptors => this opens the K+ channel
• GIRK => Inwardly rectifying K+ channel

Transporters

• Active Transport: Primary/secondary
  • Active Transport: The two types of active transports are Primary and Secondary. Primary active transport is defined by the direct use of ATP hydrolysis to supply needed energy to transport ions against their concentration gradient. Secondary active transport uses ATP indirectly by utilizing the energy created (high electrochemical concentration) resultant of primary active transport activity to move one class of ion against its gradient.
• Antiporter/Exchangers: Transports ions in opposing physical direction
  • Examples of Antiporters:
    • Sodium-Calcium Exchanger (NCX): Found in neurons, this antiporter exchanges three sodium ions for one calcium ion, playing a crucial role in maintaining calcium homeostasis.
    • Sodium-Hydrogen Exchanger (NHE): Neuronal NHEs exchange sodium ions for protons, contributing to intracellular pH regulation and cell volume control.
    • Sodium-Potassium Pump (Na+/K+ Pump) or Sodium-Potassium ATPase: actively transports three sodium ions out of the cell and two potassium ions into the cell, maintaining the resting membrane potential. Functions akin to a proton pump (atp as energy – Proton ATPase) in plant cells.

• Symport/Cotransporters: Cotransports ions in the same physical direction.
  • Examples of Cotransporters:
    • Sodium-Glucose Co-transporter (SGLT): SGLTs facilitate transport of sodium and glucose across the cell membrane.  In some neurons, SGLTs facilitate the co-transport of sodium ions (driver) and glucose across the cell membrane.Glucose is high in concentration inside, thus glucose outside the cell moves inward against its gradient in coordination with driver (Na+)
    • Excitatory Amino Acid Transporters (EAATs): EAAT1-5 are responsible for the uptake of glutamate
    • Sodium-Chloride Symporter (NCC): NCC co-transports sodium and chloride ions across the cell membrane, contributing to ion homeostasis.
    • GABA Transporters (GATs): Neuronal GATs (GAT-1 to GAT-4) reuptake of gamma-aminobutyric acid (GABA) from the synaptic cleft.
    • Dopamine Transporter (DAT): reuptake of dopamine from the synaptic cleft.
    • Norepinephrine Transporter (NET): reuptake of norepinephrine from the synaptic cleft.
    • Serotonin Transporter (SERT): reuptake of serotonin from the synaptic cleft.

Pumps

• Na+/K+ pump
  • The sodium-potassium pump is found in many cell (plasma) membranes. Powered by ATP, the pump moves sodium and potassium ions in opposite directions, each against its concentration gradient. In a single cycle of the pump, three sodium ions are extruded from and two potassium ions are imported into the cell.
  • Sodium/Potassium pump helps maintain resting potential, affects transport and regulates cellular volume.
  • For a cell to have a resting membrane potential, charge separation across membranes must be constant over time.
  • If fluxes are not equal, the charge separation across the membrane varies continually.
  • The passive movement of potassium out of the resting cell through open channels balances the passive movement of sodium into the cell.
  • The pump needs energy, energy comes from the hydrolysis of ATP
  • During periods of intense neuronal activity, the increased influx of sodium leads to an increase in sodium/potassium pump activity that generates prolonged outward current, leading to prolonged hyperpolarizing.
  • Hyperpolarization is a change in a cell’s potential that makes it more negative.
  • The export of sodium ions from the cell provides the driving force for several secondary active transporters such as membrane transport proteins, which import glucose, amino acids, and other nutrients into the cell by use of the sodium ion gradient.
  • Another important task of the Na+-K+ pump is to provide a Na+ gradient that is used by certain carrier processes. In the gut, for example, sodium is transported out of the reabsorbing cell on the blood (interstitial fluid) side via the Na+-K+ pump, whereas, on the reabsorbing (lumenal) side, the Na+-glucose symporter uses the created Na+ gradient as a source of energy to import both Na+ and glucose, which is far more efficient than simple diffusion.
  • Opening of chloride channels will bias the membrane potential toward its Nernst potential.
  • Chloride membranes typically use the energy stored in the gradients of other ions – which means they are cotransporters.
  • In some pathological conditions in adults such as epilepsy or chronic pain syndrome, the expression pattern of the chloride cotransporters may revert to that of an immature nervous system – this will lead to aberrant depolarizing responses to GABA.
• H+ pump

Signal-gated potassium channel: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2525744/

Inward rectification: https://www.ahajournals.org/doi/10.1161/01.RES.78.1.1 [as I said, I don’t think we want to address this in your chapters but I do think I should write up a short chapter that you can link to; this is just for your reference]