Spring, odd-numbered years (1/2 semester course; 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