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1 Membrane Potential 101 R. Low- 08/26/14 DRAFT. 2 Outline  Membrane Structure in Review.  Ion Channels.  Na + / K + ATPase and Intracellular / Extracellular.

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Presentation on theme: "1 Membrane Potential 101 R. Low- 08/26/14 DRAFT. 2 Outline  Membrane Structure in Review.  Ion Channels.  Na + / K + ATPase and Intracellular / Extracellular."— Presentation transcript:

1 1 Membrane Potential 101 R. Low- 08/26/14 DRAFT

2 2 Outline  Membrane Structure in Review.  Ion Channels.  Na + / K + ATPase and Intracellular / Extracellular ion concentrations.  Building a membrane Potential.  Electrochemical gradients.  Physics: Ohm’s Law / Nearnst Equation  Potassium vs Sodium.  The Action Potential: a primer.

3 3 The Plasma Membrane Morielli: CMB-2012

4 4 The Plasma Membrane as a Fluid Mosaic Ward: CMB - Membranes

5 5 Morielli: CMB-2012 Ion Channels Allow Passage of Specific Ions

6 6 Ion channels do not move ions. They simply provide a passive path for them to move according to their electrochemical gradients Morielli: CMB-2012 Ion Channels

7 7 Channels can move ions 100,000 times faster than the fastest rate of “carrier” proteins. Morielli: CMB-2012 Ion Channels Permit Rapid Movement

8 8 Ion channels can be specific for certain ions Morielli: CMB-2012 Ion Channels Are Selective

9 9 Types of Membrane Ionic Channels Non-gated channels: leakage channels open at rest Gated Channels: –Voltage-gated channels –Mechanically-gated channels –Chemically-gated channels (from outside or inside of the membrane) Neurotransmitter-activated Calcium-gated ATP-gated Cyclic nucleotide-gated About 100 different kinds of channels

10 10 Ion Channels and Membrane Potential Non-gated channels / Leakage Channels  Open at Rest / all the time. Gated Channels  Open on demand

11 11 Most Cells Have Membrane Potentials Cell typeMembrane Potential (mV) Neuron-60 Skeletal muscle-85 Cardiac muscle-90 Adipose cell-40 Thyroid cell-40 Fibroblast-10 Yeast-120 Neurospora. crassa-200 E. coli-140 Mitochondria-140 Morielli: CMB-2012

12 12 Ion Channels of Special Concern  K +  Na +

13 The “Na/K pump” splits ATP to make a Na + and K + concentration gradient as well as an electrical gradient (the electrochemical gradient) A transporter protein moves a few ions for each conformational change Ward: CMB - Membrane Transport

14 14 Intra- and Extra-cellular ionic compositions are different Intracellular Concentration Extracellular Concentration Low Na + (15 mM)High Na + (140 mM) High K + (130 mM)Low K + (4 mM) Low Cl - (5 mM)High Cl - (120 mM) Non-permeable Organic anions (128 mM) HCO 3 (12 mM)HCO 3 (24 mM)

15 15 Membrane Potential: Where we are going P = permeability  There is a metabolic pump which maintains these major ionic gradients: the Na + -K + - ATPase.  In the Steady State condition, the membrane has selective ion permeability through ion channels: (P K >>P Na ).  As a result, ionic gradients exist across the “resting” membrane.  The combination of ionic gradients and SELECTIVE permeability to potassium creates a resting membrane potential.

16 16 No permeability to ions: no voltage (potential difference) across the membrane. Creating the Membrane Potential

17 17 Plasma Membrane is Selectively Permeable to Potassium

18 18 Yin / Yang – Opposing Forces Yin: Concentration Gradient / Yang – Electrical Gradient

19 19 Opposing Forces: Chemical gradient vs electrical gradient Morielli: CMB

20 20 Steady State Chemical and electrical forces exactly balanced

21 21 The concentration of ions creating the potential difference is very small ( M) compared to bulk concentrations of ions (10 -3 M).

22 22 Exact balance of charge No Permeability Selective K + Permeability Electrical charge across the membrane: inside negative Generation of membrane Potential

23 23 V = IR Ohm’s Law

24 24 Equilibrium Potential can be easily calculated the Nernst Equation Walther Nernst Morielli: CMB

25 25 Membrane potential For an Ion With Available Channels, what If: 1/ Permeability DEcreases? 2/ Permeability Increases? 3/ Concentration Gradient Decreases? 4/ Concentration Gradient Increases?

26 Some Equilibrium Potentials Ion Outside mM Inside mM Ratio out:in E x at 37 o C mV K+K :20-80 Na :162 Ca 2+ 22x ,000:1123 Cl :1-65 Morielli: CMB

27 27 The Goldman-Hodgskin-Katz equation accounts for this by including a factor for the permeability of each ion. The permeability term includes both the number of ion channels and their individual permeabilities. Membrane potential is influenced by multiple ions Cell typeMembrane Potential (mV) Neuron-60 Skeletal muscle-85 Cardiac muscle-90 Adipose cell-40 Thyroid cell-40 Fibroblast-10 Yeast-120 Neurospora. crassa-200 E. coli-140 Mitochondria-140 Morielli: CMB

28 28 Calculation of Electrochemical Equilibrium Potentials E K = 2.3 RT log [K + ]o = 62 log 4 = - 94 mV ZF [K + ]i 130 E Na = 2.3 RT log [Na + ]o = 62 log 140= + 60 mV ZF [Na + ]i 15 E Cl = 2.3 RT log [Cl - ]i = 62 log 5 = - 86 mV ZF [Cl - ]o 120 Equilibrium potentials for each ion calculated according to the internal and external ionic concentrations described for skeletal muscle. NOT to worry about Morielli: CMB

29 29 Cell typeMembrane Potential (mV) Neuron-60 Skeletal muscle-85 Cardiac muscle-90 Adipose cell-40 Thyroid cell-40 Fibroblast-10 Yeast-120 Neurospora. crassa -200 E. coli-140 Mitochondria-140 IonOutsideInsideExEx mM mV K+K Na Ca 2+ 22x Cl Which Ions Dictate the Steady State Membrane Potential (Ex)

30 30 Addition of a Na-selective channel. A steady-state equilibrium is established Sodium Enters the Game

31 31 Cell typeMembrane Potential (mV) Neuron-60 Skeletal muscle-85 Cardiac muscle-90 Adipose cell-40 Thyroid cell-40 Fibroblast-10 Yeast-120 Neurospora. crassa -200 E. coli-140 Mitochondria-140 IonOutsideInsideExEx mM mV K+K Na Ca 2+ 22x Cl Which Ions Dictate the Steady State Membrane Potential (Ex)

32 32 Critical Nomenclature Time Hyperpolarization Depolarization Em mV Resting Em

33 33 For a Membrane where Potassium Permeability Dominates What will Happen if Sodium Channels Open?  Nothing  Depolarization  Hyperpolarization

34 34 Summary: Membrane potential  “Resting” Membrane Potential REQUIRES a Permeable Ion AND a Concentration Gradient.  In most cells, the key ion is Potassium: high Intracellular concentration PLUS available open channels*  A Steady State (Equilibrium) is reached when the Chemical and Electrical Driving Forces are matched. *P K > ˃ >P Na

35 35 What will happen to Membrane Potential if: 1/ Extracellular Potassium Concentration Rises? 2/ Intracellular Potassium Concentration Rises? 3/ Potassium Permeability Decreases? Once Again …

36 36 The Magic of the Action Potential Only certain KEY CELLS: e.g. Neurons, Skeletal Muscle, Cardiac Muscle

37 37 The Action Potential Silverthorn, Human Physiology, 5 th edition

38 38 The Action Potential and the Currents Silverthorn Human Physiology Fifth Ed.

39 39 Receptors as Ion Channels The Synapse between Neurons Cell Body Axon Putting ion Channels to work

40 40 Receptors as Ion Channels Neuromusclar Junction Neuromuscular Junction Muscle Membrane Axon Terminus Case #1 Low: CMB-Cell Signaling Putting ion Channels to work

41 41 Summary: Action Potential See Slide #38

42 42 That’s It!

43 43 Answers: Clicker Question Fodder Slide #24: Get closer to zero Slide: #25: 1/ Less Negative 2/ More Negative 3/ Less Negative 4/ More Negative Slide #33: depolarization Slide #35: 1/ Depolarozation 2/ Hyperpolarization 3/ Depolarization


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