TRANSPOTERS AND ION CHANNELS BY DINESH K M PHARM PHARMACOLOGY 1
CONTENTS INTRODUCTION TRANSPORTERS Types of transporters Membrane transporters ION CHANNELS Types of ion channels Role of ions in body REFERENCES 2
Cell membrane 3
TRANSPORTERS Transporters (membrane transport/carrier proteins) are specialized membrane-spanning proteins that assist in the movement of ions, peptides, small molecules, lipids and macromolecules across a biological membrane. 4
TYPES OF TRANSPOTERS There are two different types of transport P assive and Active Transport. In simple terms they are transport based on the energy.. So it also called as Energy independent Energy dependent 5
Passive transport Passive transport requires no energy input as transport follows a concentration gradient. It is sub-divided into two types: . Diffusion: spontaneous movement of a membrane permeable substance across the membrane. Facilitated transport: the movement of a membrane impermeable substance across the membrane via transporters 6
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Active transport In contrast active transport requires energy (usually from ATP hydrolysis) to transport substances into a cell against the concentration gradient. It is also sub-divided into two types: Primary active transport: the transport protein contains an ATPase, which hydrolyses ATP to generate the energy required for transport (sometimes called an ion pump) . Secondary active transport: in contrast there is no direct coupling of ATP but instead the potential difference created by pumping ions out of the cell by primary active transport is exploited. 8
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Membrane transporters can be also divided into three main classes; ABC transporters, P-type ATPase's and solute carrier family (SLC). ABC transporters ABC transporters are primary active transporters, which transport a wide range of substrates mainly to the outside of a cell membrane or organelle. Their substrates include: lipids and sterols, ions and small molecules, drugs and large polypeptides. ABC transporters play a critical role in the development of multi-drug resistance in cancer cells. Overexpression of ABC transporters can result in chemotherapeutics being pumped out of cell faster than they can enter. 10
• P-type ATPase are a family of transport enzymes which pump cations across the membrane using primary active transport. Examples of this family include Ca2 +-ATPase's and Na+ ,K+ -ATPase's. • The solute carrier family includes transporters that function by secondary active transport and facilitative diffusion. They are located on the cell membrane as well as on the intracellular membrane of organelles. Examples of the solute carrier family include the biogenic amine transporters (NET, DAT and SERT) and the Na+ /H+ exchanger. Inhibitors of the SLC family of transporters have proved useful in the treatment of a variety of disorders, including depression (SERT), epilepsy (GABA transporter) and Parkinson's disease (DAT). 11
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Aquaporin's Aquaporins , also called water channels , are integral membrane proteins from a larger family of major intrinsic proteins that form pores in the membrane of biological cells, mainly facilitating transport of water between cells. The cell membranes of a variety of different bacteria, fungi, animal and plant cells contain aquaporins through which water can flow more rapidly into and out of the cell than by diffusing through the phospholipid bilayer . 13
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Aquaporin inhibited is sulfhydryl-reactive compounds, including mercuric chloride and p- chloromercuribenzene sulfonate ( pCMBS ), inhibit water transport. 15
Gated ion channels There are three major groups of ion channels. Ligand gated ion channels Voltage gated ion channels Lipid gated ion channels Other gating such as Calcium activated potassium channels Inward rectifier ion channels.. etc 16
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Ligand gated ion channel 20
Voltage gated ion channel 21
Lipid gated ion channel 22
Types of ions Sodium ions are the principal cations found outside cells in the body. They help regulate and control the level of body fluids. Too little leads to diarrhea, anxiety, a decrease in body fluids, and circulatory failure. However, most people have the opposite problem—too much sodium ion—ingested mainly as table salt and salty snack foods. Too much increases water retention, leading to high blood pressure (hypertension). Potassium ions are the principal cations found inside cells in the body. Bananas, orange juice, and potatoes are good sources of Potassium ions help regulate cellular functions, including nerve impulses and heartbeats, and the level of body fluids. 23
Chloride ions are the principal anions found outside cells in the body. They serve as counterions (ions necessary to balance electrical charge) for in the extracellular fluid and for in gastric juice. Like chloride ions are ingested mainly as table salt. Like sodium and potassium ions, chloride ions are involved in maintaining acid–base and fluid balances. It is difficult to separate the effect of too much from that of too much both seem to be involved in hypertension. Too little dietary is rare, but it can result from heavy sweating, chronic diarrhea, and vomiting. Calcium ions occur mainly in the skeleton and account for 1.5–2% of body mass. is therefore essential for building and maintaining bones and teeth. Also, plays a crucial role in blood clotting, muscle contraction, and the transmission of nerve signals to cells. An adequate supply of is especially important during pregnancy and in growing children. It helps to prevent osteoporosis in older people. Good sources of calcium are milk and other dairy products, nuts, and legumes. Magnesium ions like are found mainly in the bones, but they are also vital components of many enzymes, which are substances our bodies need in order to release energy from the food we eat. Good sources of are green vegetables ( is a component of the chlorophyll in all green plants), milk, bread, cereals, and potatoes. Phosphate ions exist mainly as and in body fluids. About 85% of the phosphorus-containing ions in the body are in the bones, where they act as the counterions for Also, they play an important role in energy production from food. Good sources of phosphate are milk and other dairy products, cereals, and meat. 24
Antiport and Symport In secondary active transport, the two molecules being transported may move either in the same direction (i.e., both into the cell), or in opposite directions (i.e., one into and one out of the cell). When they move in the same direction, the protein that transports them is called a symporter , while if they move in opposite directions, the protein is called an antiporter . 25
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27 https://youtu.be/qd7a3AM_hSc
References Essential of pharmacology by kd Tripati Rang and dale’s pharmacology Web source & wikipedia Slide shares. 28