Ion Transport and Homeostasis

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Lecture 5

• Ion Transport and Homeostasis

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Please join the UT BME Department for the
worldwide movie premiere of the BME377
Internship Documentary

• Come celebrate the achievements of our
  spectacular BME undergraduates - the stars of
  this years summer internship at The Texas
  Medical Center!

Date Sept. 15, 2004 Place ACES room 2.302
Time 5 oclock
Come see how a summer can change your life!
Be among the first to screen the BME 377
documentary! Enjoy BME377 student posters. A
reception will follow the screening. Refreshments
provided. More info and the movie (after 9/15)
are available at http//www.engr.utexas.edu/bme
/faculty/richards-kortum/BME377/mission/mission.ht
m
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Special Guests

• Provost Sheldon Ekland-Olson
• Dean Ben Streetman
• Chairman Ken Diller

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Review of Lecture 4

• The Cell Membrane
• Movement Across Cell Membranes
• Membrane Proteins Signal Transduction

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EGFR

• Transmembrane receptor
• Extracellular ligand-binding domain
• Helical transmembrane domain
• Intracellular tyrosine kinase domain
• Activation of EGFR
• Epidermal growth factor (EGF) and other ligands
  bind to extracellular domain
• First step in a series of complex signalling
  pathways which take message to proliferate from
  cell membrane to genetic material within cell
  nucleus
• Heightened activity at the EGF receptor
• Can be caused by an increase in the concentration
  of ligand around cell, an increase in receptor
  numbers, a decrease in receptor turnover, or
  receptor mutation
• Leads to increase in the drive for the cell to
  replicate

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EGFR Inhibitors

• http//www.astrazeneca.com
• http//www.imclone.com/index_start.php

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Outline

• Cellular Homeostasis
• Resting Membrane Potential

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Outline

• Cellular Homeostasis
• Osmotic Equilibrium
• Chemical Equilibrium
• Electrical Equilibrium
• Cell Membrane and Ion Channels
• Resting Membrane Potential

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Cellular Homeostasis

• Cell membrane is selectively permeable
• Allows for
• Osmotic equilibrium
• Chemical disequilibrium
• Electrical disequilibrium
• End Result
• Intracellular and extracellular compartments are
  chemically and electrically different, but have
  same total concentration of solutes
• Electrochemical gradient produces electrical
  potential difference of -70 mV across membrane

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Chemical Disequilibrium

• Most solutes are restricted by transport
  properties of cell membrane
• Energy input is required to maintain chemical
  disequilibrium

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Fig 5.30 Distribution of solutes in the body
fluid compartments Silverthorn 2nd Ed
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Membrane Impermeable
Osmotic Equilibrium Electrical Equilibrium Not
Chemical Equilibrium
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Membrane Permeable to K
Osmotic Equilibrium Not Electrical
Equilibrium Not Chemical Equilibrium
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Electrical Disequilibrium

• Which ions are responsible for resting membrane
  potential?
• K generates most of resting membrane potential
• Osmotic pressure causes K to leak from cell
• Electrical gradient pulls K back in cell
• When forces are balanced, no more net movement of
  K
• Nernst Potential

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Electrical Disequilibrium

• Which ions are responsible for resting membrane
  potential?
• K generates most of resting membrane potential
• Osmotic pressure causes K to leak from cell
• Electrical gradient pulls K back in cell
• When forces are balanced, no more net movement of
  K
• Na also contributes to resting membrane
  potential, opposite sign as that due to K

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Electrical Disequilibrium

• Which ions are responsible for resting membrane
  potential?
• K generates most of resting membrane potential
• Osmotic pressure causes K to leak from cell
• Electrical gradient pulls K back in cell
• When forces are balanced, no more net movement of
  K
• Na also contributes to resting membrane
  potential, opposite sign as that due to K
• Net resting membrane potential is -70 mV

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Electrical Disequilibrium

• Four ions contribute to resting membrane
  potential
• Extracellular excess, fairly impermeable
• Na, Cl-, Ca2
• Intracellular excess, fairly permeable
• K
• Significant change in membrane potential does not
  require movement of large number of ions
• To change by 100 mV, only 1/100,000 K ions must
  move across membrane

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Outline

• Cellular Homeostasis
• Resting Membrane Potential
• Nernst Potential
• Circuit Model of Cell Membrane
• GHK Equation

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Nernst Potential

• Balance electrochemical gradients
• Ficks law to describe chemical gradient
• Ohms law to describe electrical gradient

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Circuit Model of Cell Membrane

• Single ion channel
• No net ion flow

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Multiple Ion Channels

• Goldman Equation
• Instead of Jion 0
• Now have Jnet electric current 0

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Circuit Model with Multiple Ions

• Model
• Solve using Nodal Analysis
• Active transport

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Integrated Membrane Processes

• Small changes in membrane potential act as
  signals in nonexcitable cells
• Beta cells of pancreas
• Synthesize insulin
• When blood glucose levels increase (after a
  meal), beta cells release insulin
• Insulin directs other cells to take up glucose
• How do beta cells know when to secrete insulin?
• Beta cells metabolism is linked to electrical
  activity

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Ion Channels in Beta Cells

• Voltage gated Ca2 channels
• Usually closed
• Opens when cell depolarizes
• ATP gated K channel
• Usually open
• Closed when ATP binds to it

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Summary

• Cellular Homeostasis
• Resting Membrane Potential

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Poem of the Day

• Billy Collins
• Former US Poet Laureate (2001-03)
• New York State Poet Laureate (2004-06)
• Professor of English, Lehman College,
  CCNY
• Litany

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Due Dates

• Tuesday, September 14th
• Homework 3