Ion channel RECEPTOR

PHARMACOLOGY-1
UNIT-2

1. ASSIGNMENT ON ION CHANNEL RECEPTOR SUBMITTED BY: SUBMITTED TO : MARY MELNA Dr. Kunjbihari Sulakhiya Sir ENROLL NO : 1801024022 INDIRA GANDHI NATIONAL TRIBAL UNIVERSITY ,AMARKANTAK(M.P )

2. What are ion channels? Pore forming transmembrane proteins associated with transport of specific ions in or out of the cells. Highly selective in type of ion transported (exceptions are there). Very high rate of ion transfer. Ions are transported across electrochemical gradient. Passive mechanism.

3. Biological Roles Conductance of nerve impulse,generation of action potential,synaptic ransmission . Cardiac,skeletal and smooth muscle contraction. Epithelial Transport of Nutrients and ions. T-cell activation (immune regulation). Pancreatic β -cells insulin release.

4. CLASSIFICATION

5. Classification based on gating: 1.Voltage Gated Ion Channels Open and close in response to membrane potential. 2.Ligand Gated Ion Channels Open in response to specific ligand molecules binding to the extracellular domain of the receptor protein. 3.Other Gatings Indirect signaling,mechano -gated ion channels,light gated channels

6. Voltage Gated Ion Channels Voltage sensitive Conformational change in response to the potential gradient. Generally ion specific. Important for excitable cells like neurons. Role in regulation of depolarization and polarization of neuronal membrane during an action potential. Distributed along the axon and soma of the neurons.

7. Structure of Voltage Gated Channels Voltage gated ion channels are made up of three basic parts : 1.The transmembrane pores 2.Voltage Sensor 3.Selectivity Filter Contains different subunits: α subunit and other auxillary subunits

8. Mechanism of Voltage Gated Ion Channels

9. Types of Voltage Gated Ion Channels Voltage Gated Sodium Channels (9 membrane ,responsible for membrane depolarization in action potential generation). Voltage Gated Calcium Channels (10 members ,play an important role in both linking muscle excitation with contraction as well as neuronal excitation with transmitter release). Voltage Gated Potassium Channels (40 members ,role in repolarisation of cell membrane after action potential)

10. Types of Voltage Gated Ion Channels Transient receptor Potential Channels (28 types ,some of them are voltage gated,named after their role in Drosophila phototransduction ). Hyperpolarisation -activated cyclic nucleotide-gated channels ( pacemaking channels in the heart,sensitive to cAMP , CGMP that alter the voltage sensitivity of the channels) Voltage Sensitive Proton Channels (helps in acid extrusion from cell,phagocytosis,strongly PH regulated)

11. MOA Voltage Gated Sodium Channels

12. MOA Voltage Gated Calcium Channels

13. MOA

14. MOA Transient receptor Potential Channels

15. MOA Hyperpolarization -activated cyclic nucleotide-gated channels Voltage Sensitive Proton Channels

16. Ligand Gated Ion Channels Group of transmembrane ion channels that allow the passing of several ions upon the binding of specific chemical messenger like neurotransmitters. Two domains : transmembrane domain including channel pore ,Extracellular domain including Ligand binding site. Function:Conversion of presynaptic chemical signal quickly and effectively into post-synaptic electrical signal. Three super families:cys -Loop Receptors,Ionotropic Glutamate Receptor,ATP Gated Channels.

17. Cys -Loop Receptors Characteristic loop formed by a disulfide bond between two cystine residues in the N terminal extracellular domain. Provides specificity for : Acetylcholine,sertonin,glycine,glutamate and γ - aminobutyric acid (GABA) in vertebrates. Structural elements are well conserved,with a large extracellular domain(ECD) haboring an alpha-helix and 10 beta-strands .

18. Inotropic Glutamate Receptor Bind to NT glutamate. Consists of a tetramer. Each subunit consists of extracellular amino terminal domain,an extracellular ligand binding domain,a transmembrane domain. Each subunit of the tetramer has a binding site for glutamate .

19. ATP Gated Channels Bind to ATP in order to open. They form trimers with two transmembrane helices per subunit and both the C and N terminate on the intracellular side.

20. Structure:

21. Classification on the basis of types of ions passed: Chloride channels Potassium channels Sodium Channels Calcium Channels Proton Channels

22. Classification on the basis of Localisation Plasma Membrane Channels Examples- Voltage-Gated potassium channels,Sodium Channels,Calcium Channels and Chloride Channels. Intracellular Channels Example- ER Channels, Mitochondrial Channels.

23. Drugs Targeting Ion Channels Ion channels are varied widely and play a wide range of critical biological functions. 55 different medical conditions have been attributed to ion channel dysfunction. Owning to these conditions,13.4% of all drugs are targeted to ion channels (second highest after GPCRs). Worldwide sale of ion channel drugs(estimate)>$12 billion .

24. Drugs Targeting Ion Channels Tetrodotoxin Ziconitide Benzodiazepines Conotoxin Lidocaine Other drugs are:Verapamil,Diltiazem,Amlodipine,Nimodipine,Nifedipin,Lidocaine etc.

25. Ion Channel dysfunction and Diseases Channelopathies Cystic fibrosis is caused by mutations in the CFTR gene,which is a Chloride Channel. Brugada syndrome is another ventricular arrhythmia caused by voltage-gated sodium channel gene mutations. Shaker gene mutations, ataxia etc.

26. THANKYOU!

27. Questions related to ion channel receptors: 1. Which of the following statements is true about transmembrane electrical potential? a) The chemical gradient drives Cl – and K + inwards b) The electrical gradient drives Na + and Ca +2 inwards c) The chemical gradient drives Na + and Ca +2 inwards and K + outward d) The chemical gradient drives Cl – and K + outwards Answer: c Explanation: The chemical gradient drives Na + and Ca +2 inwards and K + outward, electrical gradient drives Cl – . 2. The receptor channels for which of the following are gated by extracellular ligands ? a ) Glycine b) IP 3 c) cAMP d) cGMP Answer: a Explanation: The receptor channels for glycine are gated by extracellular ligands .

28. 3. Voltage regulation means a) Na + /K + pumps controls potential b) Unless the voltage is regular gates will not respond c) Oscilloscope only can control potential d) With changes in the membrane potential voltage gated ion channels open and close Answer: d Explanation: With changes in the membrane potential voltage gated ion channels open and close, this is regulation of voltage. 4. Which of the following statements is false about a ligand -gated ion channel receptor? a) They are present in the cell membrane b) They consist of five glycoproteins c ) Differences in membrane potential affect whether the channel receptors are open or close d) Neurotransmitters can act as the chemical messengers for these channels Answer: c Explanation: Ligands affect whether the channel receptors are open or close in a ligand -gated ion channel whereas voltage gated ion channels are controlled by the differences in membrane potential affect .

29. 5. Nicotinic acetylcholine receptor is an example of a) Ligated gated receptor channel b) Serpentine receptors c) Adhesion receptors d) Receptor enzyme Answer: a Explanation: Nicotinic acetylcholine receptor is an example of ligated gated receptor channel .