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    Cell Physiology1.

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    khorrami4
    This document provides an overview of cell physiology, beginning with a description of the plasma membrane. It notes the fluid mosaic model of the membrane and discusses the roles of lipids and proteins. Several cellular organelles are mentioned, including lysosomes and their involvement in various storage diseases. The document then covers topics like transport mechanisms, membrane potential, action potentials, and neurotransmission. It provides details on ion channels, neurotransmitters, receptors, and the roles of various molecules like glutamate, GABA, and calcium in cellular signaling pathways.

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    Cell Physiology1.

    Uploaded by

    khorrami4
    219 views118 pages
    This document provides an overview of cell physiology, beginning with a description of the plasma membrane. It notes the fluid mosaic model of the membrane and discusses the roles of lipids and proteins. Several cellular organelles are mentioned, including lysosomes and their involvement in various storage diseases. The document then covers topics like transport mechanisms, membrane potential, action potentials, and neurotransmission. It provides details on ion channels, neurotransmitters, receptors, and the roles of various molecules like glutamate, GABA, and calcium in cellular signaling pathways.

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    I hope it is useful for different fields of medicine

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    This document provides an overview of cell physiology, beginning with a description of the plasma membrane. It notes the fluid mosaic model of the membrane and discusses the roles of lipids and proteins. Several cellular organelles are mentioned, including lysosomes and their involvement in various storage diseases. The document then covers topics like transport mechanisms, membrane potential, action potentials, and neurotransmission. It provides details on ion channels, neurotransmitters, receptors, and the roles of various molecules like glutamate, GABA, and calcium in cellular signaling pathways.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    219 views118 pages

    Cell Physiology1.

    Uploaded by

    khorrami4
    This document provides an overview of cell physiology, beginning with a description of the plasma membrane. It notes the fluid mosaic model of the membrane and discusses the roles of lipids and proteins. Several cellular organelles are mentioned, including lysosomes and their involvement in various storage diseases. The document then covers topics like transport mechanisms, membrane potential, action potentials, and neurotransmission. It provides details on ion channels, neurotransmitters, receptors, and the roles of various molecules like glutamate, GABA, and calcium in cellular signaling pathways.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 118

    In the name of GOD

    Physiology of the cell


    by

    H. Khorrami Ph.D.
    http://khorrami1962.spaces.live.com http://www.scribd.com/khorrami4 khorrami4@yahoo.com

    Contents:
    Plasma membrane Some cellular organells 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 G-proteins Apoptosis & necrosis Muscle fiber, neuromuscular junction, contraction, twitch, motor unit, Isometric & isotonic contraction Muscle metabolism, fatigue

    Inner life of the cell

    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

    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

    Fluid mosaic model

    Lipids 42%
    Phospholipid Cholesterol Glycolipid

    Membrane lipids

    Phospholipids

    Lipids

    Fatty acids

    Omega-3
    Common name Hexadecatrienoic acid (HTA) Alpha-linolenic acid (ALA) Stearidonic acid (SDA) Eicosatrienoic acid (ETE)

    Lipid name 16:3 (n-3)

    Chemical name all-cis 7,10,13hexadecatrienoic acid

    18:3 (n-3)
    18:4 (n-3) 20:3 (n-3)

    all-cis-9,12,15-octadecatrienoic acid
    all-cis-6,9,12,15,octadecatetraenoic acid all-cis-11,14,17-eicosatrienoic acid all-cis-8,11,14,17eicosatetraenoic acid all-cis-5,8,11,14,17eicosapentaenoic acid all-cis-6,9,12,15,18heneicosapentaenoic acid

    Eicosatetraenoic acid (ETA)


    Eicosapentaenoic acid (EPA, Timnodonic acid) Heneicosapentaenoic acid (HPA)

    20:4 (n-3)
    20:5 (n-3) 21:5 (n-3) 22:5 (n-3) 22:6 (n-3) 24:5 (n-3) 24:6 (n-3)

    Docosapentaenoic acid (DPA, Clupanodonic acid) Docosahexaenoic acid (DHA, Cervonic acid)
    Tetracosapentaenoic acid Tetracosahexaenoic acid (Nisinic acid)

    all-cis-7,10,13,16,19docosapentaenoic acid
    all-cis-4,7,10,13,16,19docosahexaenoic acid all-cis-9,12,15,18,21tetracosapentaenoic acid all-cis-6,9,12,15,18,21tetracosahexaenoic acid

    Omega-6
    Common name Lipid name 18:2 (n-6) 18:3 (n-6) 20:2 (n-6) 20:3 (n-6) 20:4 (n-6) 22:2 (n-6) 22:4 (n-6) 22:5 (n-6) 24:4 (n-6) 24:5 (n-6)
    Chemical name all-cis-9,12-octadecadienoic acid

    Linoleic acid Gamma-linolenic acid (GLA) Eicosadienoic acid Dihomo-gammalinolenic acid (DGLA) Arachidonic acid (AA) Docosadienoic acid Adrenic acid Docosapentaenoic acid (Osbond acid) Tetracosatetraenoic acid Tetracosapentaenoic acid

    all-cis-6,9,12-octadecatrienoic acid

    all-cis-11,14-eicosadienoic acid

    all-cis-8,11,14-eicosatrienoic acid all-cis-5,8,11,14-eicosatetraenoic acid all-cis-13,16-docosadienoic acid all-cis-7,10,13,16-docosatetraenoic acid all-cis-4,7,10,13,16docosapentaenoic acid all-cis-9,12,15,18tetracosatetraenoic acid all-cis-6,9,12,15,18tetracosapentaenoic acid

    Omega-9

    Common name Oleic acid Eicosenoic acid

    Lipid name 18:1 (n-9) 20:1 (n-9)

    Chemical name cis-9-octadecenoic acid cis-11-eicosenoic acid all-cis-5,8,11-eicosatrienoic acid cis-13-docosenoic acid cis-15-tetracosenoic acid

    Mead acid
    Erucic acid Nervonic acid
    Monounsaturated

    20:3 (n-9)
    22:1 (n-9) 24:1 (n-9)

    Phospholipids' head groups

    Fatty acid tails

    Glycolipids

    Cholesterol

    Membrane asymmetry

    Organelle lipids

    Lateral organization

    Membrane curvature

    Transport of lipids

    Lipid synthesis

    Non-vesicular lipid transport

    Movements in membrane
    Phlip-phlap Rotation Lateral diffusion ( 107 per second) Flexion

    Functions of carbohydrates
    Negative surface charge Attachment of cells together As receptor Immune recognition

    Lysosomes
    Lysosomal storage
    disease(LSD) Pompe MPS Tay-Sachs Gout Leprosy, silicosis, -glucosidase Many enzymes Hexosaminidase A Hypoxanthine-guaninephosphoribosyl-tansferase Glycogen in hepatocytes Glycosaminoglycans Gangliosid Uric acid Enzyme involved Problem

    Na: 145 Cl: 104 K: 5 Ca: 10-3 Hco3


    -

    Na: 15 Cl: 4 K: 150

    Mg
    PO4+ AA Fat Pco2 Protein PH: 7.00

    Glucose

    Po2
    PH: 7.40

    Osmosis
    Osmolarity(volume) Osmolality(weight) Isotonic, hypotonic & hypertonic

    Osmosis

    Osmotic pressure
    Based on decrease in freezing point A one molar solute -1.86 C Plasma -0.52 280mmol pv=nRT, p1=162.63310 A one molar solute 19200mmHg Osmotic pressure of plasma? 5600mmHg

    Could a hyperosmolar solution be isotonic?


    Yes Because tonicity depend on permeability of the membrane

    Membrane transport
    Diffusion Facilitated diffusion Active transport

    Simple & facilitated diffusion

    Simple diffusion No saturation Fast

    Facilitated diffusion Saturation(Vmax) Low velocity

    Chemical gradient
    Linear correlation

    Carrier protein
    Non-linear correlation Competition

    Diffusion
    Ficks law:
    J = - DA(dc/dx)
    Flux=
    . ( in-Cout)

    D: diffusion coefficient(cm2/sec) X: diffusion distance

    Secondary active transport


    Symport
    Intestine Kidney Glucose & AA

    Antiport
    Heart Rbc Calcium, H+, HCO3, Cl-

    Ion Channels
    Leak channels Voltage-gated channels Ligand-gated channels
    Intracellular Extracellular

    Mechanically-gated channels

    Sodium channel

    Glucose transporters
    transporter tissue function insulin stimulation

    GT-1 GT-2 GT-3 GT-4 GT-5

    Facilitative glucose transporters BBB, Rbc, fibroblast glu uptake liver, cell, intestine low-affinity brain, fibroblast glu uptake fat, skl. muscle, heart glu uptake small intestine, sperm fruc. transp. Active glucose transporters intestine, kidney intes. renal reabs

    + ? +++ ?

    SGT-1

    Resting potential

    Resting potential

    Action potential

    Na-voltage gated channel

    Na channel

    Sodium channel

    Action potential

    Action potential equations


    Nernst:
    Ek= -RT/ZF Ln [K]i/ [K]o

    Goldman-Hodgkin:
    Ek= -RT/ZF Ln P[K]i+ P[Na]i+ P[cl]o/ P[K]o+ P[Na]o+ P[cl]i

    Nernst equation

    Goldman equation

    Threshold

    Na channel

    Review

    Falling phase

    Undershoot

    Refractory period

    Resting state

    Depolarising phase

    Repolarizing phase

    Undershoot

    Blocking the channel

    Potassium channels in AP
    Delayed rectifier K ch
    In repolarization

    Early K ch
    Reduce the velocity of depolarization

    Calcium-activated K ch
    Preventing repetitive stimulation

    K channel

    Synapse

    Century 21st

    Comparison of synapses
    Electrical
    Bidirectional No delay Fast

    Chemical
    Unidirectional Delay (1-2ms) Slow

    Electrical synapse

    Gap junction

    Gap junction

    Cell to cell junctions

    Tight junction

    Zonula adherens

    Functions of the electrical transmission


    1.Electrical synapses are more reliable, less likely to fail. 2.Greater speed important in rapid reflexes involving escape reactions. 3.The synchronization of electrical activity of groups of cells. 4.Intracellular transfer of molecules such as Ca, ATP and cAMP. 5.The activity of gap junctions between cells in the retina can be modulated by dopamine. Thus the gap junctions can be dynamic components of neuronal circuits. 6. Mutations in the genes encoding gap junction proteins cause diseases: Peripheral neuropathy Charcot-Marie-Tooth disease Abnormal cardiac development Congenital deafness Charcot-Marie-Tooth disease inherited peripheral neuropathy -degeneration of peripheral nerves -Foot deformities, muscle wasting, distal sensory loss, decreased tendon reflexes Gap junction is necessary for radial migration in the neocortex

    Chemical synapse

    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.

    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

    2/27/2010

    95

    Neurotransmitters
    Small molecules
    Ach Biogenic amines
    Dopamine Norepinephrine Epinephrine 5-HT Histamine

    Neuropeptides
    Opioid peptides
    Leucine enkephalin Methionine enkephaline b - endorphin Dynorphins

    Pituitary peptide
    Oxytocin Vasopressin ACTH TSH

    Amino acids
    Aspartate GABA Glutamate Glycine Homocystein Taurine

    Nucleotides
    Adenosine ATP Retrograde gases Nitric oxide Carbon monoxide
    2/27/2010

    Gastrointestinal peptides CCK Sub-P Neurotensin Gastrin Insulin Glucagon Somatostatin

    Others
    Angiotensin Bradykinin

    Neuropeptide Y
    96

    Receptors of NTs
    Ionotropic: ligand gating i.e. nicotinic receptor (inhibited by curare) Metabotropic: work by second messenger (G protein)

    2/27/2010

    97

    Neuropharmacology of some receptors


    Neurotransmitter Acetylcholine(Ach) Receptor subtype Nicotinic receptor Muscarinic receptor AMPA NMDA Agonist Nicotine Muscarine Antagonist Curare Atropine

    Glutamate

    AMPA NMDA

    CNQX AP5

    GABA

    GABAA GABAB

    Muscimol Baclofen

    Bicuculine Phaclofen

    Acetylcholine metabolism

    Catecholamines

    Serotonin synthesis

    Glutamate receptor
    Non-NMDA; kainate receptor & AMPA
    permeability to Na & K Excitatory Act on this receptor at rest

    NMDA; Gating channel is permeable to Na, K, Mg & Ca2+ Magnesium block Act on this receptor when depolarized

    (voltage-dependent)

    N-Methyl-D-Aspartate , -amino-3-OH-5-methyl-4-isoxasole propionate


    2/27/2010 102

    Glutamate receptors

    Calcium can trigger


    Enzymatic activity Opening of a variety of channels Gene expression Cell death Long-term memory

    Glutamate receptors
    Activation of AMPA Na+ inward & K+ outward Depolarization Pop out of Mg2+ from the pore of NMDA

    Voltage-dependent NMDA

    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

    Nicotinic receptor

    Acetylcholine (N)

    Acetylcholine receptors

    Name Muscarinic

    Location End of postgang. parasym

    Blocked by Atropine

    Agonists Metacholine Carbachol Betanechol Pilocarpine Nicotine

    Nicotinic

    Autonomic ganglia Adrenal medulla N-M junction

    Scopolamine Hexamethonium Tubocurarine

    Ach (muscarinic receptor)

    TTX

    Length constant

    Conduction velocity

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