Understanding the concept of Membrane Channels

Komal Bavaskar, Mumbai university

Gap junction structures were first discovered and characterized in 1953, due to the increased resolution of the transmission electron microscope. Bernard Katz and Ricardo Miledi used noise analysis to confirm the presence of ion channels in the 1970s. It was later shown more directly using an electrical recording technique known as the “patch-clamp,” which earned Erwin Neher and Bert Sakmann, the technology’s creators, a Nobel Prize. Peter Agre discovered the water channel by chance in 1992 & was awarded the Nobel Prize in Chemistry in 2003 for his contribution.

Membrane channels are also known as transmembrane channels. They are usually quaternary protein structures (formed by two or more peptide chains which can be the same or distinct, are connected by weak non-covalent bonds) that regulate the movement of small molecules, water, or ions through membranes. Electrochemical gradients are used in membrane channels to transport ions and molecules across the membrane without using energy. Membrane channels are transmembrane proteins that can respond to chemical and physical changes in their surroundings. They serve a wide range of functions. It can be divided into water channels, ion channels, etc.

 Aquaporins (AQPs), are membrane water channels that play an important function in regulating cell water content. These channels may be found in microbes, plants, and mammals, among other domains of life. More than 10 distinct aquaporins have been found in the human body, and impaired activity of these channels has been linked to several diseases. AQP proteins form tetramers in the cell membrane, but each monomer generates a hydrophilic pore in its center and serves as a water channel by itself. Although all AQPs are water channels, certain AQPs also permit glycerol, urea, and other small nonpolar molecules to pass through. they are also known as Aquaglyceroporins. AQPs play a role in the control of water flow across biological membranes & their expression & activity is influenced by the organism’s hydration condition. AQP function depends on cellular location & cellular milieu, it also increases water transport rate, prevents other molecules to enter.

Ion channels are molecular machines that govern cellular excitability by integrating and regulating electrical signals. There are over 300 types of ion channels but a majority of them fall into 4 types – ligand-gated, voltage-gated, mechanical-gated channels, gap junction. Important functions such as action potential generation and propagation are done using these channels.

Ligand-gated ion channels, also known as ionotropic receptors, are transmembrane ion-channel proteins that open to enable ions like Na+, K+, Ca2+, and/or Cl to flow through the membrane in response to the ligand-binding i.e., neurotransmitter to a receptor. Acetylcholine, GABA, and serotonin are some exp. of neurotransmitters. Ligand-gated ion channels are essential in rapid synaptic transmission in the nervous system and are activated when a neurotransmitter binds to the ion channel. On channel activation, membrane potential gets depolarized or hyperpolarized due to some factors which lead to quick response allowing ions to flow down their electrochemical gradient. For exp, 1) Nicotinic acetylcholine receptor, is involved in cholinergic transmission in both the central and peripheral nervous systems. The channel becomes permeable to Na⁺ and K⁺ ions when acetylcholine binds to its binding sites, resulting in a net inflow of sodium, producing depolarization and an electrical excitatory effect. 2) GABA is involved in the central nervous system (CNS). The ion channel becomes permeable to chloride ions when GABA binds to the receptor. Hyperpolarization occurs as a result of the net inflow of chloride ions. Inhibitory effects on nerve transmission are elicited by GABA receptors in the CNS.

Voltage-gated ion channels, (VGICs), are activated by changes in the electrical properties of the membrane it is embedded in. The inner section of the membrane is generally at a negative voltage. Some of these channels have a predetermined threshold voltage that determines whether the channel is open or closed. Other voltage-gated channels, which open and close at varying voltages, are more intricate. For exp, the gate may open at a certain positive value, but once open, it will not close until a specific negative voltage is reached. Some voltage-gated channels have several gates, each of which responded to a distinct voltage property. For ions to pass across the membrane in this sort of channel, both gates must be open. VGICs are categorized as voltage-gated sodium, potassium, calcium, or chloride channels. Voltage-gated Na⁺and K⁺ channels are primarily present in the neuron’s axon hillock and axon. Voltage-gated Ca⁺⁺ channels are present in axon terminal bulbs and are responsible for vesicle fusion with the cell membrane and neurotransmitter release. Chloride channels are present in plasma membranes and intracellular organelles. 

Mechanically gated channels, open due to the physical deformation of the cell membrane. These channels are mainly are involved with the sense of touch (somatic-sensation). For example, when pressure is applied to the skin, these channels open, allowing ions to enter the cell. A channel that opens in response to temperature variations, such as when checking the water in the shower.

Gap junction is also known as cell-to-cell channels. These are consisting of hemichannel or connexons, which are connected end to end across the membrane. Each connexin consists of 6 polypeptide units called connexins. They allow the movement of not only inorganic ions but also organic ions like sugar amino acids. The transverse 2 membranes of contiguous cell and connect the cytoplasm of an adjacent cell. For exp, 1) intercellular communication – cardiac muscle cells use gap junctions to spread action potential to nearby cells. This allows the heart to generate a single, continuous and forceful contraction that pumps the blood throughout the body. 2)Cell nourishment – cells that are found far away from capillaries use gap junctions to receive nutrients such as glucose 3) Embryological development.

Diseases related: –

• Gap junction:
• Cerebrovascular diseases such as brain ischemia and brain hemorrhage, neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, epilepsy, and brain tumors, the embryo could not develop normally.
• Connexin disorders – skin abnormalities like keratitis-ichthyosis deafness syndrome, erythrokeratodermia variabilis, Vohwinkel’s syndrome, hypotrichosis-deafness syndrome.
• Ion & water channels:
• Channelopathies & aquaporinopathies are caused by a genetic defect in ion & water channels respectively.
• Mutations in muscle – hyper & hypokalemic periodic paralysis, myotonias, long QT syndrome, Brugada syndrome, malignant hyperthermia, and myasthenia.
• Neuronal disorders – epilepsy, episodic ataxia, familial hemiplegic migraine, Lambert-Eaton myasthenic syndrome, Alzheimer’s disease, Parkinson’s disease, schizophrenia, and hyperekplexia.
• Kidney disorders – Bartter’s syndrome, polycystic kidney disease, and Dent’s disease.
• Secretion disorders – hyperinsulinemic hypoglycemia of infancy and cystic fibrosis.
• Vision disorders – congenital stationary night blindness and total color blindness.
• Aquaporinopathies – neuromyelitis optica, an autoimmune neuroinflammatory disease, nephrogenic diabetes insipidus, congenital cataracts.

Also read: Tarantula toxin- the Key to Future Chronic pain medications?

References:

1. Membrane Channel Types – https://cnx.org/contents/oOdtYHPj@2/Membrane-Channel-Types
2. Structure, Dynamics, and Function of Aquaporins – https://www.ks.uiuc.edu/Research/aquaporins/
3. The thumbnail image and image 2 in the article have been taken from Servier Medical Art (smart.servier.com).

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