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Ion Channel Receptors

by

Dr. TAMSEELA MUMTAZ

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ION CHANNEL RECEPTER

  • Ion channel receptors are usually multimeric proteins located in the plasma membrane. Each of these proteins arranges itself so that it forms a passageway or pore extending from one side of the membrane to the other.
  • These passageways, or ion channels, have the ability to open and close in response to chemical or mechanical signals.
  • When an ion channel is open, ions move into or out of the cell in single-file fashion.

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Con..

Individual ion channels are specific to particular ions, meaning that they usually allow only a single type of ion to pass through them.

Both the amino acids that line a channel and the physical width of the channel determine which ions are able to wiggle through from the cell exterior to its interior, and vice versa.

The opening of an ion channel is a fleeting event. Within a few milliseconds of opening, most ion channels close and enter a resting state, where they are unresponsive to signals for a short period of time.

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Certain cells, commonly called excitable cells, are unique because of their ability to generate electrical signals. Although several types of excitable cells exist including

neurons

muscle cells,

and touch receptor cells all of them use ion channel receptors to convert chemical or mechanical messages into electrical signals.

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An excitable cell maintains a different concentration of ions in its cytoplasm than exists in its extracellular environment. Together, these concentration differences create a small electrical potential across the plasma membrane. Then, when conditions are right, specialized channels in the plasma membrane open and allow rapid ion movement into or out of the cell, and this movement creates an electrical signal.

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How Are Electrical Signals Propagated:-

The opening of ion channels alters the charge distribution across the plasma membrane. Recall that the ionic composition of the cytoplasm is quite different from that of the extracellular environment.

For instance, the concentration of sodium ions in the cytoplasm is far lower than that in the cell's exterior environment. Conversely, potassium ions exist at higher concentrations within a cell than outside it.

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Such differences create a so-called electrochemical gradient, which is a combination of a chemical gradient and a charge gradient.

The opening of ion channels permits the ions on either side of the plasma membrane to flow down this dual gradient.

This ion flow results in the production of an electrical signal. The actual number of ions required to change the voltage across the membrane is quite small.

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  • In excitable cells, the electrical signal initiated by ion channel receptor activity travels rapidly over the surface of the cell due to the opening of other ion channels that are sensitive to the voltage change caused by the initial channel opening.

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DIFFERECE:-

Electrical signals travel much more rapidly than chemical signals, which depend on the process of molecular diffusion. As a consequence, excitable cells respond to signals much more rapidly than cells that rely solely on chemical signals . In fact, an electrical signal can traverse the entire length of a human nerve cell — a distance of as much as one meter — within only milliseconds.

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CLASSIFICATION

Based on the stimulus to which they respond, ion channels are divided into three superfamilies':

  • voltage-gated,
  • ligand-gated
  • mechano-sensitive ion channels.

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  • Voltage-gated ion channels:

The opening and closing of the voltage-gated ion channels are dependent on the membrane potential..

Voltage-gated channels respond to perturbations in cell membrane potential, and are highly selective for a specific ion, i.e., Na+, K+, Ca2+, and Cl-. They are further subdivided into families based on the major permeant ion.

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Voltage-gated Na+ channel

These channels are responsible for the generation of action potentials of long duration, and thus are targets of local anesthetics, such as lidocaine and benzocaine.

Also responsible for the rapid influx of sodium ions during the action potential in nerves, muscle and endocrine cell.

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STRUCRURE:

  • GATE
  • VOLTAGE SENSOR
  • SELECTIVITY FILTER

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Voltage-gated Ca2+ channels

They regulate intracellular Ca2+ concentrations, and thus are responsible for a wide range of biochemical processes within cells. One of the most important processes regulated by these channels is the release of neurotransmitters at synapses. Calcium channel blockers are valuable in treating a variety of conditions ranging from heart disease to anxiety disorders.

It regulate intra cellular processes such as contraction, secretion and neurotransmission.

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Voltage-gated K+ channels

They constitute the largest and the most diverse class of voltage-gated ion channels. They are imperative in generating the resting membrane potential.

Voltage-gated Cl- channels

These channels are present in every type of neuron and are involved in regulating excitability and cell volume. They are also known to contribute to the resting membrane potential.

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  • Ligand-Gated Ion Channels (LGIC)

These channels are also known as the ionotropic receptors and get opened in response to specific ligand molecules binding to the extracellular domain of the receptor proteins. Binding of the ligand causes a conformational change in the channel protein that ultimately leads to the opening of the channel gate and subsequent ion flux across the plasma membrane occurs.

LGIC are targets for many drugs, such as anesthetics, antipsychotics, and antidepressants. They are named according to the ligand to which they respond.

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P2X Receptors:--

They are the most recently discovered membrane ion channels. They are preferably permeable to Na+, K+ and Ca2+ and are activated by ATP. P2X receptors are widely expressed in many tissues and are shown to play key roles in various physiological processes, such as nerve transmission, pain sensation, and various inflammatory responses.

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  • Mechano-Sensitive Ion Channels:

Ion channels responding to changes in mechanical forces on the cell membrane are termed mechano-sensitive ion channels. These channels are involved in detection and transduction of external mechanical forces into electrical and/or chemical intracellular signals.

Mechano-sensitive ion channels are involved in regulation of blood pressure and cell volume, stimulation of muscle and bone development, and the senses of hearing and touch.

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  1. Mechanosensitive ion channels are gated ion channels that respond to mechanical deformation of the plasma membrane. A mechanosensitive channel is connected to the plasma membrane and the cytoskeleton by hair-like tethers. When pressure causes the extracellular matrix to move, the channel opens, allowing ions to enter or exit the cell.
  2. Stereocilia in the human ear are connected to mechanosensitive ion channels. When a sound causes the stereocilia to move, mechanosensitive ion channels transduce the signal to the cochlear nerve.

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References: