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Ion Channels - Definition, Types, Description of Sodium, Calcium-Potassium and Chloride Ion Channels

Updated on July 15, 2018
 Diagram of an Ion Channel: 1 - channel domains (typically four per channel), 2 - outer vestibule, 3 - selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 - cell membrane.
Diagram of an Ion Channel: 1 - channel domains (typically four per channel), 2 - outer vestibule, 3 - selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 - cell membrane. | Source

Welcome to ePharmacology. Today our topic is "Ion Channels".

Ion channels - Definition of ion channels

What are ion channels? Definition of ion channels

Ion channels are pores that open and close in an all-or-nothing fashion on time scales of 0.1 to 10 ms to provide aqueous channels through the plasma mem­brane that ions can traverse. There are a number of drugs which act by modulat­ing the ion channels.

Types of ion channels

Ion channels are either voltage-sensitive or ligand-gated.

Ion channels that are normally modulated by membrane potential are known as voltage-sensitive ion channels. Voltage-sensitive ion channels mediate the conductance of sodium, calcium, and potassium. They provide rapid changes in ion permeability. These channels exhibit high ion selectivities, voltage sensitivities, and single-channel conductance.

The S4 transmembrane domain of a voltage-gated ion channel embedded in a membrane is thought to be a helical structure which contains a large number of cationic residues. The cationic residues are postulated to be paired with anionic sites which may reside on nearby transmembrane helices (S1 -S3 or S5 or S6). A change in transmembrane voltage may then cause the S4 helix to twist upward which results in the net movement of a positive charge from the intracellular region to the extracellular region. This could be responsible for the gating current observed prior to current flow through the ion pore. Presumably the movement of the S4 helix is then coupled to movement of residues which allow the opening of the ion pore.

Some types of ion channels
Some types of ion channels | Source

Sodium channel

The voltage-sensitive sodium channel plays the critical role in initiation of the action potential. Activation of the channel results from abrupt changes in mem­brane potential, and channel opening allows for the inward movement of sodium from the extracellular compartment. The permeability to sodium rapidly rises and then slowly declines even when the potential is maintained.

The voltage-sensitive sodium channel has been purified (a mass of about 300 KDa). It has three subunits- α, β1 and β2. α subunit is large and has a molecular weight of 260 kDa. On the other hand, the β subunit has molecular weight of about 33 and 36 kDa. The α subunit is heavily glycosylated and contains four repeating domains forming a central transmembrane pore.

Neuronal, cardiac muscle and skeletal muscle sodium channels differ slightly in structure and pro­tein composition.

The activation of these channels can be blocked by the toxins like saxitoxin, tetrodotoxin, and scorpion α-toxin. On the contrary, batrachotoxin and veratridine stimulate the influx of sodium.

Tetrodotoxin can block neuronal and skeletal muscle sodium channels at concentrations as low as 10 nM but the concentration required to block cardiac muscle sodium channels is 100 times higher.

Local anesthetics and antiarrhythmic drugs (class I) act by interacting with the sodium channels. But the site of action of local anesthetic is different from the site of action of tetrodotoxin.

Voltage gated sodium channels
Voltage gated sodium channels | Source

Calcium channel

Calcium channels of plasma membrane are of two types: receptor-operated calcium chan­nels and voltage-sensitive calcium channels.

Influx of calcium through receptor-operated calcium channel is directly coupled to occupation of a receptor. NMDA recep­tor appears to involve this type of calcium channel. Voltage-sensitive calcium channels open and allow the entry of calcium when there is rapid depolarization of the cell membrane. The channel is made up of four or five subunits. The α1 subunit (A, B, C, D, E, G, H, or I) controls the selectivity of the conductance pore for calcium entry, the voltage sensor, and the gating mechanism.

There are three distinct types of voltage-sensitive calcium channels – L (also known as α1C orCav1.2), N (also known as α1B or Cav2.2) and T (also known as α|G, α1H, α11 or Cav3.1, Cav3.2, Cav3.3).

L-type channel is long-opening, high-conductance and is activated at -30 to +20 mV. This type of calcium channel is found in heart, cardiac-conducting tissue, and vascular smooth muscle.

First generation L-type calcium channel antagonists- nifedipine, verapamil, and diltiazem- are from three distinct classes and cause vasodilatation, slowing of cardiac conduction, and nega­tive ionotropic effect. Second and third generation L channel antagonists -nimodipine, nicardipine, felodipine, and amlodipine - have more effect on vascular dilatation than on myocardial contractility or cardiac conduction.

N-type calcium channel is responsible for the calcium entry that triggers neu­rotransmitter release. Here, the calcium conductance is medium and is found in neuronal tissue. N-type calcium channel antagonists include ω-conotoxin GVIA, MVIIA, and CVID.

T channel has low calcium conductance and is rapidly repolarized. They are opened at low (-80 to -30 mV) membrane potential. This type of channel is found in brain, neuronal, and cardiovascular tissues. Selective T-type calcium channel antagonist is mibefradil.

Subunit assembly and subtypes of voltage-gated calcium channels
Subunit assembly and subtypes of voltage-gated calcium channels | Source

Potassium channel

There are varieties of potassium channel and their conductances are regulated by membrane potential, receptor ligands, intracellular calcium, and ATP.

ATP- sensitive potassium channels are opened when the intracellular ATP concentra­tion is decreased. Sulphonylureas act by modulating the potassium channels. Block of potassium channel by sulphonylurea causes the β-cells of the pancreas to depolarize, thus stimulating insulin secretion.

The vasodilator effect of cromokalim in smooth muscle is due to opening of the potassium channel leading to hyperpo­larization the cell.

X-ray analysis with data to 3.2 angstroms reveals that four identical subunits create an inverted teepee, or cone, cradling the selectivity filter of the pore in its outer end. The narrow selectivity filter is only 12 angstroms long, whereas the remainder of the pore is wider and lined with hydrophobic amino acids. A large water-filled cavity and helix dipoles are positioned so as to overcome electrostatic destabilization of an ion in the pore at the center of the bilayer. Main chain carbonyl oxygen atoms from the potassium channel signature sequence line the selectivity filter, which is held open by structural constraints to coordinate potas­sium ions but not smaller sodium ions. The selectivity filter contains two potas­sium ions about 7.5 angstroms apart. This configuration promotes ion conduction by exploiting electrostatic repulsive forces to overcome attractive forces between potassium ions and the selectivity filter. The architecture of the pore establishes the physical principles underlying selective potassium conduction.

Structure of potassium channels
Structure of potassium channels | Source
Types of potassium channels
Types of potassium channels | Source

Chloride channel

Most benzodiazepines act to facilitate the opening of the chloride channel by GABA.

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