Course Syllabus

 

The Cellular Physiology of Disease: Excitable cells and the molecules that make them work.

 

Spring 2007

 

Dr. Julio Fernandez, 1011A Fairchild Bldg, jfernandez@columbia.edu, 854-9141

Class room: 1000 Fairchild

Class time: Tuesday and Thursday 4:00-5:15 pm

Recitations: Arun Wiita, TBA

 

Course Description:

            This course will present a quantitative description of the cellular physiology of excitable cells (mostly nerve and muscle).  While the course will focus on examining basic mechanisms in cell physiology, there will be a thread of discussion of disease mechanisms throughout.  The end of each lecture will include a discussion of the molecular mechanisms of selected diseases that relate to the topics covered in the lecture.  The course will consist of two lectures per week.  This course will be of interest to advanced (3000-4000 level) undergraduates that aim to pursue careers in medicine as well as those that will pursue careers in biomedical research. This course will also be of interest to graduate students desiring an introduction to the cellular physiology of nerve and muscle.       

The first part of the course will cover the electrical equivalent circuit of cells and the structure, kinetics and detection of single ion channels and how they integrate to give rise to a cell's electrical properties.  We will discuss the "patch-clamp" technique for single cell and single ion channel recording in some detail.  We will discuss excitability in nerve and muscle.   

The second part will cover the molecular mechanisms of vesicular exocytosis and synaptic transmission.  We will discuss exocytosis by histamine secreting mast cells, catecholamine secreting chromaffin cells, and synapses.   We will discuss the use of patch-clamp technique and electrochemical detection techniques to study vesicular exocytosis and synaptic transmission at the single cell level.  We will discuss secretory mechanisms in the gut.   

The final part of the course will cover the mechanisms of force generation in biology.  Our focus will be to cover the molecular mechanisms of muscle contraction.  We will also cover the techniques used to measure force at the single protein level.  For example, we will discuss in some detail the use of "optical tweezers" in studies of the activity of single myosin motors, and use of atomic force microscopy (AFM) in studies of the giant elastic protein titin, responsible for muscle elasticity.

Tuesdays will be full lectures;  Starting from the second week of class, Thursday's will focus on the discussion of two important papers related to the topic of the week's lecture.  Small groups of student will be responsible for presenting and will be graded for their understanding of their assigned papers.  There will be one midterm and one final.  Grades will be assigned based on paper discussions, the midterm and the final.

 

Prerequisites: One 3000 level course in Cell Biology or Biochemistry or the instructor’s permission.

 

 

Reading Material

Required

  1. Aidley, “The Physiology of Excitable Cells", Cambridge University Press, Cambridge, UK, 2001.
  2. Jonathon Howard "Mechanics of Motor Proteins and the Cytoskeleton", Sinauer Associates, Inc, Sunderland Massachusetts, 2001
  3. (Optional)   Keynes and Aidley, “Nerve and Muscle”, Cambridge University Press, Cambridge, UK, 2001.  ( An excellent overview and study guide)

 

Tentative schedule

 

Date

Aidley chapter

Howard

chapter

Topic

 

 

 

Part 1: Ion channels and cellular excitability

Jan 16

1,2

 

Experimental methods in molecular physiology

Jan. 18

 

 

Electrical properties of the resting cell membrane I

Jan. 23

3

 

Electrical properties of the resting cell membrane II

Jan. 25

 

 

Presentations

Jan. 30

3

 

Cable theory and the action potential in excitable cells

Feb. 1

 

 

Presentations

Feb. 6

4

 

The ionic basis of the action potential

Feb. 8

 

 

Presentations

Feb. 13

5

 

Voltage dependent ion channels

Feb. 15

 

 

Presentations

Feb. 20

6

 

Ion channels and disease

Feb. 22

 

 

Presentations

 

 

 

Part 2: Vesicular Exocytosis

Feb. 27

7

 

Fast synaptic transmission

Mar. 1

 

 

Presentations

Mar. 6

8

 

Neurotransmitter gated ion channels

Mar. 8

 

 

Presentations

Mar. 13

10

 

Molecular mechanisms of vesicular exocytosis

Mar. 15

 

 

Presentations

Mar. 20

 

 

Spring Break

Mar. 22

 

 

Spring Break

Mar. 27

 

 

Midterm

 

 

 

Part 3:  Molecular Mechanics

Mar. 29

18,19

 

Molecular architecture of the contractile mechanism

Apr. 3

 

 

Presentations

Apr.  5

20

 

Electrical activation of muscle

Apr. 10

 

 

Presentations

Apr. 12

 

12,13

Structure and dynamics of motor proteins

Apr. 17

 

 

Presentations

Apr.  19

 

15

Steps and Forces of single motor proteins

Apr.  24

 

 

Presentations

Apr.  26

 

 

Reverse Engineering of titin, the elastic protein of muscle

May. 1

 

 

Presentations

May. 10

 

 

Final exam