• Ion Channels

Lecture 1 –Nernst Equation, Ohm’s Law, Patch ClampPermeation and Gating

Learning Objectives 1. Know the classes of all membrane transport proteins and distinguish them according to

rates of transport.2. Know the transporter reconstitution into liposomes method of studying the transport

process. 3. Describe Glucose transport through GLUT1 transporters as an example of a uniport-

catalyzed transport system. Know the mechanism thought to account for transport through uniporters.

4. Understand how distribution of unbalanced charges at the membrane boundary accounts for membrane potentials.

5. Know the distribution (low vs. high) of the four major ions in most mammalian cells. 6. Know the thermodynamic derivation of the Nernst Equation and be comfortable explaining it

qualitatively. 7. Given a membrane potential be able to determine the flow of ions (for a particular

distribution in and out of the cell) considering the relative magnitude and direction of the chemical and electrical forces.

8. Be able to use Ohm’s law to determine the currents flowing through the cell membrane. 9. Given a membrane potential be able to determine the flow of ions (for a particular

distribution in and out of the cell) considering Ohm’s Law.10. Know the different types of Ion Channels and the major features they possess. 11. Understand how the balance of currents determines the membrane potential.12. Know the voltage clamp and all modes of the patch clamp techniques. 13. Predict how ion flux through a particular ion channel will influence the

membrane potential.14. Understand how K ion selectivity, permeation and gating occurs.

From: Structure and function of facilitative sugar transporters.

Barrett et al, Current Opinion in Cell Biology 11, 496-502 (1999).

Distribution of Ions and theResting Potential

Na+ = 145 mM

Ca++ = 2 mM

K+ = 5 mM

Cl- = 125 mM

Na+ = 15 mM

Ca++ = .0001 mM

K+ = 145 mM

Cl- = 10 mM

Equlibrium potentials for major permeable ionic species

In myocytes:ENa = 61.5 log (145/15) = + 60 mV

ECa = 61.5 log (2/.0001) = + 131 mV

ECl = -61.5 log (125/ 10) = - 67 mV

EK = 61.5 log (5/ 145) = - 89 mV

Atomic Resolution StructuresSelectivity and Permeation

Atomic Resolution StructuresGating

Inwardly rectifying K channels

Permeation pathways of Kir3.4 in a “closed” state and Kv1.2 in an “open” state

From Nishida et al., 2007 EMBO J 26:4005-4015

PIP2 and the cytoplasmic gates