Almost all living cells in the human body express proteins that act as a pathway for charged ions from dissolved salts, and other ions like sodium, calcium, potassium, and chloride to pass through the lipid cell membrane, which is otherwise impermeant. This protein channel is known as the ion channel. A few of the physiological processes that involve the ion channel are the contraction of skeletal muscles and the heart, the functioning of cells in the nervous system, and secretion in the pancreas. Moreover, the cytoplasmic calcium concentration is regulated and specific subcellular compartments like lysosomes are acidified in the membranes of intracellular organelles by ion channels.
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The passive flow of ions toward equilibrium, through channels, may be driven either by chemical (concentration) gradients or by electrical (voltage) gradients. An evolutionary advantage has been provided to single-celled organisms due to the development of the ion channels. Due to the ability to alter ion flow, these organisms regulate their volume despite the environmental changes.
Electrical signalling and cellular secretion have also been aided by ion channels through subsequent evolution. Multimeric proteins, usually known as ion channel receptors are located in the plasma membrane. Each of these ion channel receptors extends from one end of the membrane to the other by arranging itself to form a pore or passage. Most of the ion channels are gate-like, that is, they open and close spontaneously, or sometimes to respond to a specific stimulus like any change in voltage across the membrane which the charged segments of the channel protein (voltage-gated ion channels) senses, or when a small molecule is being bound to the channel protein (ligand-gated ion channels).
In most ion channels, it is found that they are quite selective and allow only certain ions to pass through. The selection of ions can be based on:
the type of ions, that is, a single type of ions (for example potassium ions) are permitted only
while other channels select relatively, that is, they allow only a specific charge of ions (for example positively charged cations) to pass through and prohibiting the other charge (negatively charged anions here).
The gating properties and selectivity highly vary in the cells of higher organisms. Such cells may also express more than a hundred varieties of ion channels receptors.
The charged ions flow through the open channels and represent an electric current. These currents alter the distribution of charge and the voltage across the membrane is changed. The voltage-gated channels present in excitable cells allow a transient influx of positive ions like that of calcium and sodium. For the deep polarization of the membrane ion channels underlie action potentials. Action potentials allow coordination and precise timing of physiological outputs by being transmitted rapidly, over a long distance. From nearly all cases, it is found that downstream physiological effects are triggered by action potentials by opening calcium-selective, voltage-gated ion channels and elevating the intracellular concentration of calcium. Such effects involve secretion or muscle contraction.
About many types of ion channel proteins, their amino acid sequence has been discovered, and in some cases, the X-ray crystal structure of the channel is determined as well. With respect to the structure, most of the ion channels can be classified into six or seven superfamilies.
In the case of potassium-selective channels, which are one of the best-characterized ion channels, a tunnel-like structure, also known as the conducting pore, is formed by four homologous transmembrane subunits. This tunnel acts as a polar pathway through the non-polar, lipid membrane.
In other types of ion channels, a central conducting pore is generated by either three or five homologous subunits.
The polarized water molecules stabilize the ions in the solution in the surrounding environment. On the other hand, the less selective channels form pores. These pores have enough diameter to pass the ions and water molecules through them, together.
At the molecular level, from the ongoing basic research on ion channels, we can understand the structural basis of permeability, gating, and ion selectivity. Researchers also tend to answer queries regarding the cellular regulation of ion channel protein synthesis, and also, about the subcellular distribution and ultimate degradation of ion channels. Besides all of these, researchers also show that compounds with greater potency and specificity for channels involved in cardiovascular disease, pain sensation, and other pathological conditions are capable of sourcing drug development.
1. What Diseases are Related to Ion Channels?
Answer: In the ion channel genes with inherited mutations and in genes which encode proteins, that regulate the activity of ion channel have been implicated in numerous diseases. Such diseases include diabetes mellitus, cardiac arrhythmias (irregularities in heartbeats), certain types of epilepsy, and ataxia, which is the inability to coordinate voluntary muscle movements. For instance, genetic variation in potassium-selective and sodium-selective channels, or in their associated regulatory subunits, leads to some forms of the long-QT syndrome. In this syndrome, there is a prolonged depolarization time-course of cardiac myocyte action potentials, which leads to fatal arrhythmias. The adenosine triphosphate (ATP)-sensitive potassium channels control the secretion of insulin from the cells in the pancreas and mutations in these channels underlie some sort of diabetes mellitus.
2. What are the Effects of Toxins on Ion Channels?
Answer: Ion channels are targeted by many natural toxins. A few examples include:
Tetrodotoxin, which is produced by bacteria that reside in puffers (or blowfish) and other organisms. They block the voltage-gated sodium channel.
Alpha-bungarotoxin, the irreversible nicotinic acetylcholine receptor antagonist. It is found in the venom of snakes in the genus Bungarus (kratis).
D-tubocurarine and strychnine, which are alkaloids derived from plants. The neurotransmitters glycine and acetylcholine open the activation of ion channels which are obstructed by the strychnine and D-tubocurarine respectively.
A variety of therapeutic drugs, including benzodiazepines, local anaesthetics, and sulfonylurea derivatives, acts directly or indirectly to modulate the activity of the ion channel.