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  • 1. Resting Membrane Potential
  • 2. QuickTime™ and a Cinepak decompressor are needed to see this picture.
  • 3. Cell Membranes F5-1 • Cell membrane distinguishes one cell from the next. • Cell membranes do the following: • a) Regulates exchange of salts, nutrients and waste with the environment. • b) Mediate communication between the cytosol and environment. • c) Maintain cell shape.
  • 4. Fig. 03.02
  • 5. Uneven Distribution of Solutes Amongst Body Compartments •Solutes are molecules which dissolve in liquid. Cell membranes prevent most solutes from diffusing amongst compartments. • Active transport of solutes helps create and maintain differences in solute concentrations. • The body is kept in a state of chemical disequilibrium. F5-28
  • 6. Ion Intracellular Extracellular Normal Plasma Value K+ 150 5 3.5-5.0 Na+ 12 140 135-145 Cl- 10 105 100-108 Organic Anions 65 0 Uneven Distribution of Major Ions in the Intracellular and Extracellular Compartments (mM) T5-9 • The body is in a state of electrical disequilibrium because active transport of ions across the cell membrane creates an electrical gradient. • Although the body is electrically neutral, cells have excess negative ions on the inside and their matching positive ions are found on the outside.
  • 7. Terminology Associated with Changes in Membrane PotentialF8-7, F8-8 • Depolarization- a decrease in the potential difference between the inside and outside of the cell. •Hyperpolarization- an increase in the potential difference between the inside and outside of the cell. • Repolarization- returning to the RMP from either direction. •Overshoot- when the inside of the cell becomes +ve due to the reversal of the membrane potential polarity.
  • 8. Resting Membrane Potential (Difference) • The resting membrane potential is the electrical gradient across the cell membrane. • Resting: the membrane potential has reached a steady state and is not changing. • Potential: the electrical gradient created by the active transport of ions is a source of stored or potential energy, like chemical gradients are a form of potential energy. When oppositely charged molecules come back together again, they release energy which can be used to do work (eg. molecules moving down their concentration gradient). • Difference: the difference in the electrical charge inside and outside the cell (this term is usually omitted)
  • 9. K+ Ions Contribute to the Resting Membrane Potential F5-33 • In electrical equilibrium and chemical disequilibrium. • Membrane is more permeable to K+ ions. • K+ leaks out of the cell down its concentration gradient. • Excess -ve charge buildup inside the cell as Pr- cannot cross the membrane. An electrical gradient is formed. • The -ve charges attract K+ ions back into the cell down the electrical gradient. • Net movement of K+ stops. The membrane potential at which the electrical gradient opposes the chemical gradient is known as the equilibrium potential (E). EK= -90 mV.
  • 10. Nerst Equation • The equilibrium potential is calculated using the Nerst equation: in out ion [I] [I] ln Fz RT E = (mV) R= gas constant (8.314 jules/o K.mol) T= temperature (o K) F= Faraday constant (96, 000 coulombs/mol) z= the electric charge on the ion [I]out= ion concentration outside the cell [I] in= ion concentration inside the cell • Derived under resting membrane conditions when the work required to move an ion across the membrane (up its concentration gradient) equals the electrical work required to move an ion against a voltage gradient.
  • 11. RMP Dependence on [K+ ]o
  • 12. F5-34 Contribution of Na+ to the Resting Membrane Potential • Membrane permeable to Na+ only. • Same principles hold as in the case of K+ movement across the membrane. • The equilibrium potential for Na+ is, ENa= +60 mV.
  • 13. Goldman Equation • It is used to calculate the membrane potential resulting from all the participating ions when Vm is not changing: outClinNainK inCloutNaoutK m ][ClP][NaP][KP ][ClP][NaP][KP lnV −++ −++ ++ ++ = ζΦ ΡΤ • PX= the relative permeability of the membrane to ion X (measured in cm/s). An ion’s contribution to the membrane potential is proportional to its ability to cross the membrane. • PK: PNa: PCl= 1.0: 0.04: 0.45 at rest.
  • 14. Electrodiffusion Model of the Cell Membrane Ix = z2 F2 VmPx RT [X]i −[X]oe −zFVm / RT( ) 1−e −zFVm / RT( ) ⎛ ⎝ ⎜ ⎞ ⎠ ⎟ GHK Current Eqn.: Current of ion X through the membrane
  • 15. I-V Relationship Predicted by GHK Current Equation
  • 16. Direction of Current Rectification is Dependent On The Ratio of Ion Concentration On Both Sides Of The Membrane As Predicted by GHK Current Equation
  • 17. Vrev = (61.5mV)*log10 [K+ ]o +α[Na+ ] [K+ ]i +α[Na+ ] ⎛ ⎝ ⎜ ⎞ ⎠ ⎟ RMP Dependence on [K+ ]o And α
  • 18. Resting Membrane Potential in Real Cells • Most cells are 40x more permeable to K+ than Na+. As a result, the resting membrane potential is much closer to EK than ENa. • In actual cells, the resting membrane potential is much closer to -70 mV because a small amount of Na+ leaks into the cell. • The Na+ is pumped out and the K+ pumped in by the Na+ /K+ -ATPase. It pumps 3 Na+ ions out and 2 K+ ions in. F5-35 • Na+ /K+ -ATPase is also known as an electrogenic pump because it helps maintain an electrical gradient. 7-20% of the RMP is generated by the pump. • Not all transporters are electrogenic pumps: •Na+ /K+ /2Cl- symporter moves one +ve charge for every -ve charge. • HCO3 - /Cl- antiport in red blood cells moves these ions in a one-for-one fashion.
  • 19. Electrical Model of the Cell Membrane
  • 20. References 1. Boron, W.F. & Boulpaep, E.L. (2005). Medical Physiology: Elsevier. Ch.3 & 6 2. Tortora, G.J. & Grabowski, S.R (2003). Principles of Anatomy & Physiology.New Jersey: John Wiley & Sons. Ch.12, pp.396-398. 3. Silverthorn, D.U (1998). Human Physiology: An Integrated Approach. New Jersey: Prentice Hall. Ch.5, pp.131-133, 136-141. 4. Johnston, D. & Wu, S. (1999). Foundations of Cellular Neurophysiology: Cambridge, Mass.:MIT Press. Ch.2

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