Biochemistry and Molecular Biophysics Graduate Group

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BMB 624 - Molecular and Biophysical Basis of Ion Channel Diseases

Spring, odd-numbered years (1/2 credit)

Course Directors:
Roland Kallen, M.D., Ph.D., rgk@mail.med.upenn.edu
Zhe Lu, Ph.D., zhelu@mail.med.upenn.edu

Course goals: Examine the structure-function aspects of ion channels (especially channel gating and ion selectivity) and investigate examples of mutations in channels that result in inherited diseases.

Format: Assignment and discussion of hallmark papers in the field, student presentations and critical discussion with an occasional lecture, there will be some homework problems and a final exam.

Reference Texts for initial lectures:   

Ion Channels and Disease by Frances M. Ashcroft  2000 Academic Press
Ion Channels of Excitable Membranes (3rd Edition) by Bertil Hille 2001 Sinauer Press

Topics:

Class 1: Introduction - Studying Ion Channels
Class 2: Na Channels
Class 3: Na Channels

Introduction: Membrane potential & structure; reversal potential; equations (Nernst, GHK, Boltzmann); electrophysiological protocols; data collection and interpretation (simple kinetic schemes). Steady-state activation, inactivation; single channel studies; use of toxins; probes of structure; mutant cycle analysis. Channel structure: current views

Class 4: K channels
Class 5: K channels

K+ conduction and selectivity, and voltage gating.

Class 6: Ca channels
Class 7: No class
Class 8: Thanksgiving vacation
Class 9: Ca Channels

Voltage-gated Ca2+ channels: purification/cloning, subunit composition, properties, physiology and CaV-related genetic diseases. Non voltage-gated Ca2+-permeable channels with focus on the TRP family.

Class 10: Ligand Gated Channels
Class 11: Ligand Gated Channels

Neurotransmission, transmitters, acetylcholine receptors, GABA receptors and glutamate receptors. Discussion of two short reviews on acetylcholine receptors and glutamate receptors (Sine and Engel (2006) Nature 440:448; Mayer (2006) Nature 440: 456. Ernst et al. (2005) Mol Pharmacol 68:1291

Class 12: Channelopathies
Class 13: Channelopathies

Periodic paralysis, Long QT syndrome, Epilepsies, Endplate disease, etc.

Class 14: Problem Set #1
Class 15: Exam