Cell physiology1.
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this presentation is about cell membrane, transmembrane transport, resting potential and action potential
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Cell physiology1.
- 1. Physiology of the cell by H. Khorrami Ph.D. http://www.scribd.com/khorrami4 https://www.slideshare.net/khorrami4 khorrami4@yahoo.com
- 2. Contents: • Plasma membrane • Transport across membrane • Membrane potential: resting & action potential • Refractory period • Chronaxie, rheobase, length constant, • Synapses, electrical & chemical • EPSP, IPSP • Adaptation, plasticity, post tetanus potentiation, long term potentiation • Lateral inhibition, synaptic fatigue, • Receptive field • Summation: temporal, spacial • Signal transduction • Apoptosis & necrosis • Muscle fiber, neuromuscular junction, contraction, twitch, motor unit, • Isometric & isotonic contraction • Muscle metabolism, fatigue
- 3. Inner life of the cell
- 6. Cell membrane • Two layer phospholipids ( 45% of weight) • 2 × 1.7 + 0.1 nm • Proteins ( 55% of weight) • + 2 × 2nm • Structural • Integral • Channel • Pump • Enzymes • Receptors • Orphan • Non-orphan • Carbohydrates
- 10. Properties of membranes • Hydrophobic barriers between aqueous compatments(cytosol & organelles) • Flexible, formed into different shapes • Selectively permeable to small molecules, not charged or large • Specialized protein complexes to control impermeant molecules • Store energy as concentration gradients – Voltage(nerve cells) – PH, K, Na and Ca gradients
- 13. Lipids 42% • Phospholipid • Cholesterol • Glycolipid
- 14. Membrane lipids
- 15. Phospholipids
- 16. Lipids
- 19. Fatty acids
- 20. Omega-3 Common name Lipid name Chemical name Hexadecatrienoic acid (HTA) 16:3 (n-3) all-cis 7,10,13- hexadecatrienoic acid Alpha-linolenic acid (ALA) 18:3 (n-3) all-cis-9,12,15-octadecatrienoic acid Stearidonic acid (SDA) 18:4 (n-3) all-cis-6,9,12,15,- octadecatetraenoic acid Eicosatrienoic acid (ETE) 20:3 (n-3) all-cis-11,14,17-eicosatrienoic acid Eicosatetraenoic acid (ETA) 20:4 (n-3) all-cis-8,11,14,17- eicosatetraenoic acid Eicosapentaenoic acid (EPA, Timnodonic acid) 20:5 (n-3) all-cis-5,8,11,14,17- eicosapentaenoic acid Heneicosapentaenoic acid (HPA) 21:5 (n-3) all-cis-6,9,12,15,18- heneicosapentaenoic acid Docosapentaenoic acid (DPA, Clupanodonic acid) 22:5 (n-3) all-cis-7,10,13,16,19- docosapentaenoic acid Docosahexaenoic acid (DHA, Cervonic acid) 22:6 (n-3) all-cis-4,7,10,13,16,19- docosahexaenoic acid Tetracosapentaenoic acid 24:5 (n-3) all-cis-9,12,15,18,21- tetracosapentaenoic acid Tetracosahexaenoic acid (Nisinic acid) 24:6 (n-3) all-cis-6,9,12,15,18,21- tetracosahexaenoic acid
- 21. Omega-6 Common name Lipid name Chemical name Linoleic acid 18:2 (n-6) all-cis-9,12-octadecadienoic acid Gamma-linolenic acid (GLA) 18:3 (n-6) all-cis-6,9,12-octadecatrienoic acid Eicosadienoic acid 20:2 (n-6) all-cis-11,14-eicosadienoic acid Dihomo-gamma-linolenic acid (DGLA) 20:3 (n-6) all-cis-8,11,14-eicosatrienoic acid Arachidonic acid (AA) 20:4 (n-6) all-cis-5,8,11,14-eicosatetraenoic acid Docosadienoic acid 22:2 (n-6) all-cis-13,16-docosadienoic acid Adrenic acid 22:4 (n-6) all-cis-7,10,13,16-docosatetraenoic acid Docosapentaenoic acid (Osbond acid) 22:5 (n-6) all-cis-4,7,10,13,16-docosapentaenoic acid Tetracosatetraenoic acid 24:4 (n-6) all-cis-9,12,15,18-tetracosatetraenoic acid Tetracosapentaenoic acid 24:5 (n-6) all-cis-6,9,12,15,18-tetracosapentaenoic acid
- 22. Omega-9 Common name Lipid name Chemical name Oleic acid† 18:1 (n-9) cis-9-octadecenoic acid Eicosenoic acid† 20:1 (n-9) cis-11-eicosenoic acid Mead acid 20:3 (n-9) all-cis-5,8,11-eicosatrienoic acid Erucic acid† 22:1 (n-9) cis-13-docosenoic acid Nervonic acid† 24:1 (n-9) cis-15-tetracosenoic acid †Monounsaturated
- 24. Cholesterol
- 25. Glycolipids
- 26. Functions of carbohydrates • Negative surface charge • Attachment of cells together • As receptor • Blood group • Immune recognition(MHC)
- 29. Na: 15 Cl: 4 K: 150 Mg PO4 + AA Fat Pco2 Protein PH: 7.00 Na: 145 Cl: 104 K: 5 Ca: 10-3 Hco3 - Glucose Po2 PH: 7.40
- 30. Osmosis
- 31. Osmotic pressure
- 32. Osmotic pressure • Based on decrease in freezing point • A one molar solute -1.86⁰ C • Plasma… -0.52o C • 280mmol /L • pv=nRT, p×1=1×62.63×310 • A one molar solute 19200mmHg • Osmotic pressure of plasma? • 5600mmHg
- 35. Could a hyperosmolar solution be isotonic? • Yes • Because tonicity depend on permeability of the membrane
- 36. Total body water: 60% of body weight 40-42 L Intracellular fluid: 40% of body weight 25-28 L Extracellular fluid: 20% of body weight 14-15 L
- 39. Membrane transport • Diffusion • Facilitated diffusion • Active transport
- 43. Simple & facilitated diffusion Simple diffusion Facilitated diffusion No saturation Saturation(Vmax) Fast Low velocity Chemical gradient Carrier protein Linear correlation Non-linear correlation Competition
- 44. Glucose transporters transporter tissue function insulin stimulation • Facilitative glucose transporters • GT-1 BBB, Rbc, fibroblast glu uptake + • GT-2 liver,β cell, intestine low-affinity - • GT-3 brain, fibroblast glu uptake ? • GT-4 fat, skl. muscle, heart glu uptake +++ • GT-5 small intestine, sperm fruc. transp. ? • Active glucose transporters • SGT-1 intestine, kidney intes. renal reabs -
- 45. Sodium channel
- 46. Active transport
- 47. Active Transport
- 48. Secondary active transport • Symport – Intestine – Kidney – Glucose & AA • Antiport – Heart – Rbc – Kidney – Calcium, H+, HCO3, Cl- …
- 51. Goldman equation
- 52. Nernst equation
- 55. Gradients
- 57. Action potential
- 58. Threshold
- 60. Resting state
- 63. Undershoot
- 67. Hypokalemia, Causes • Alcohol use (excessive) • Chronic kidney disease • Diabetic ketoacidosis • Diarrhea • Vomiting • Diuretics (water retention relievers) • Corticosteroids • Excessive laxative use • Excessive sweating • Folic acid deficiency • Hyperaldosteronism
- 68. Hypokalemia, Sign & Symptoms • Muscle cramp • Fatigue • Arrhythmia • Constipation • Myasthenia( muscle weakness) • Hypertension • Flaccid paralysis • Myalgia • Respiratory depression, respiratory acidosis • Hyporeflexia
- 69. Hyperkalemia, Causes • Kidney problem • Medications • Trauma, Tissue damage, hemolysis • Alcoholism • Burns, muscle fiber damage.. • Toxins, hemolysis • Dehydration • Heart failure • Diabetes Type I( insulin dependent) • Addison’s disease • Internal bleeding
- 70. Hyperkalemia • Is a life threatening disorder • Tiredness or weakness • Numbness or tingling in limbs • Nausea or vomiting, abdominal pain • Breathing problems • Chest pain • Palpitations, arrhythmia or irregular heartbeats • If extreme, paralysis or heart failure
- 71. Synapse
- 72. Comparison of synapses Electrical Chemical Bidirectional Unidirectional No delay Delay (1-2ms) Fast Slow Heart, Retina, NS(HC, Thalamus,..) N-M junction, CNS
- 73. Electrical vs. Chemical Synapse
- 75. Chemical synapse • Neurotransmitter • Depolarization of the presynaptic nerve terminal • Triggers the release of molecules Interact with receptors on the postsynaptic neuron • Excitation or inhibition of the postsynaptic neuron.
- 76. 76 Neurotransmitters: Definition: • Synthesized by presynaptic neuron • Released by stimulation • Microapplication of NT. Mimic the presyn. stimulation • Presynaptic & microappl. Stim. Must be blocked by pharmacologic agent • High affinity uptake mechanism for the substance in synaptic terminal release of NT, synapsin
- 77. 77 Neurotransmitters • Small molecules Ach Biogenic amines Dopamine Norepinephrine Epinephrine 5-HT Histamine Amino acids Aspartate GABA Glutamate Glycine Homocystein Taurine Nucleotides Adenosine ATP Retrograde gases Nitric oxide Carbon monoxide • Neuropeptides Opioid peptides Leucine enkephalin Methionine enkephaline b - endorphin Dynorphins Pituitary peptide Oxytocin Vasopressin ACTH TSH Gastrointestinal peptides CCK Sub-P Neurotensin Gastrin Insulin Glucagon Somatostatin Others Angiotensin Bradykinin Neuropeptide Y
- 78. 78 Receptors of NTs • Ionotropic: ligand gating i.e. nicotinic receptor (inhibited by curare) • Fast • Mostly excitatory • Metabotropic: work by second messenger (G protein) • Slow • Excitatory or inhibitory
- 79. Neuropharmacology of some receptors Neurotransmitter Receptor subtype Agonist Antagonist Acetylcholine(Ach) Nicotinic receptor( in N-M) Muscarinic receptor(in Parasympathetic NS, heart) Nicotine Muscarine, pilocarpin,.. Curare Atropine Glutamate AMPA NMDA AMPA NMDA CNQX AP5 GABA GABAA GABAB Muscimol Baclofen Bicuculine Phaclofen
- 80. Acetylcholine receptors Name Location Blocked by Agonists Muscarinic End of postgang. parasym Atropine Metacholine Carbachol Betanechol Pilocarpine Nicotinic Autonomic ganglia Adrenal medulla N-M junction Scopolamine Hexamethonium Tubocurarine Nicotine
- 81. Curare
- 84. Catecholamines
- 86. Drugs on Cholinergic Synapses
- 90. Calcium can trigger • Enzymatic activity • Opening of a variety of channels • Gene expression • Long-term memory • Cell death
- 93. Excitotoxicity • High demand of brain cells to oxygen & glucose • Cardiac arrest, stroke, ….. • Limits of ATP • Depolarizing the membrane • Calcium leak into cells • Glutamate release • Depolarization • More calcium • …………… • Cell death
- 94. TTX