MOLECULAR & CELLULAR
NEUROBIOLOGY
Master Course Cognitive Neuroscience - Radboud
University, Nijmegen
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Chapter 2: Cells and within cells |
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A quote from two eminent electrophysiologists in the study of ion channels: "Our ability to do gymnastics, to perceive a colorful world, and to process language relies on rapid communication among neurons. Such signaling, the fastest in our bodies, involves electrical messages produced as ion channels in cell membranes open and close. Various ion channels mediate sensory transduction, electrical "computations", propagation over long distances, and synaptic transmission." |
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A general overview will be given of ion channels, what they are and what they do. Ion channels are membrane bound proteins which allow ions to flow into or out of cells. They are usually constructed from 4 or 5 different protein subunits. These subunits form a ring the center of which is an ion pore. Shown here is an ion channel on the membrane constructed from individual subunits. The arrow is showing the pore through which ions will flow if the channel is open. |
Ion channels in action There are two major classes of ion channels, those that are induced to open through the binding of a ligand and those that are induced to open by a change in membrane potential. The first group are referred to as ligand-operated or ligand-gated ion channels. The second group are referred to as voltage-operated or voltage-gated ion channels. On the right is a side view through the middle of a ligand-operated channel. The ligand (green circle) binds to specific sites in extracellular side of the ion channel. As a consequence of this binding "gates" deep within the receptor are induced to open and thus ions can flow through the channel. Ligands are usually small molecules neurotransmitters such as acetylcholine, glutamic acid or gamma aminobutyric acid (GABA). For the second major class of ion channels, the voltage operated channels, there are no ligand binding sites. Rather, these ion channels possess voltage sensors (structure with positive charges in figure to left). With membrane depolarization (yellow arrows) the voltage sensors move and, in doing so, induce opening of an ion gate on the intracellular side of the channel. Ions are now free to flow into or out of the cell (in this example the channel is a Na+ channel and thus Na+ flows into the cell). Ion channels are constructed from discrete proteins called "subunits". Voltage-operated channels are generally constructed from 4 subunits whereas ligand-operated ion channels are constructed from 5 subunits. Shown is a representation of voltage-operated and ligand-operated channels where each subunit is represented by a cylinder in the lipid bilayer (blue circles and red tails represent phospholipids of the bilayer). By looking straight down on the channel, depicted on the far right, you can get an impression of the size of the pore (indicated as white circle). Note that because the ligand-operated channel has more subunits its pore is larger than that of a voltage-operated channel. Because of the larger pore the ligand-operated channel is, in general, less ion specific that the voltage-operated channel. For example, one of the very important ligand-operated ion channels is the so-called NMDA receptor. This receptor is a Ca2+ channel but a considerable amount of Na+ also enters the cell via the receptor when the channel has opened. |
Specificity and direction of ion flow
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Opening of Ca2+ and Na+ channels cause the cell to become less negative inside, thus a depolarization and an activation of the cell. Opening of K+ and Cl- channels cause the cell to become more negative inside, thus a hyperpolarization and an inhibition of the cell. Note that the Cl- ion, like the K+ ion, travels with the chemical gradient and against the electro-gradient. In some cells the electrochemical equilibrium point for Cl- is such that Cl- flows in fact out of the cell (against the concentration gradient!) In this case opening of the Cl- channel leads to a depolarization and activation of the cell rather than the normal hyperpolarization and inhibition of the cell. This again illustrates the importance, for each cell, to consider the electochemical equilibrium point and not just the concentration gradient of an ion when considering what the ion will do when the ion channel opens. |
How is the resting potential achieved?
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Next page: Tyrosine kinase receptors | Go back to: Receptor mechanisms |
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