Welcome to the 2008-09 MSTP PHYSIOLOGY COURSE WEBPAGE Class Time: 10:15 am to 11:45 am Location: Belfer 708 The official course schedule can be downloaded here as a .pdf. Additionally, the course schedule seen below is supplemented with lecture slides and articles/readings associated with the lecture. Enjoy the course. NOTE: Some of the files are rather large (5-10 MB) and may take some time to download. Try to be patient. Thanks. Lecture/ Date Topic/Files Lecturer Lecture 1 9/2/08 Introduction Akabas Lecture 2 9/3/08 Nonelectrolytes: Passive Flow Finkelstein Lecture 3 9/5/08 Nonelectrolytes: Active Transport Supplemental Membrane Transporter Structure Readings Structure and mechanism of the lactose permease of E. coli. (2003) Abramson et al., Science 301:610-615 Finkelstein Lecture 4 9/8/08 Ions: Membrane Potentials Finkelstein Lecture 5 9/10/08 Ions: Action Potentials Finkelstein Lecture 6 9/12/08 Ion Channels: Structure-Function The structure of the potassium channel: Molecular basis of K+ conduction and selectivity. (1998) Doyle et al., Science 280:69-77 Supplemental Potassium Channel Structure Readings Crystal structure and mechanism of a calcium-gated potassium channel. (2002) Jiang et al., Nature 417:515-522 The open pore conformation of potassium channels. (2002) Jiang et al., Nature 417:523-526 Finkelstein Lecture 7 9/15/08 Water Permeability Fraternal Twins: AQP1 and GlpF. V.M. Unger, (2000) Nature Struc. Biol. 7:1082-1084 Structural Determinants of water permeation through aquaporin-1. Murata et al., (2000) Nature 407:599-605 Finkelstein Lecture 8 9/17/08 Synaptic Transmission Akabas Lecture 9 9/19/08 Membrane Receptors and Second Messenger Systems The neurobiology of slow synaptic transmission. Greengard, P. (2001) Science 294:1024-1030 Structure of rhodopsin and the superfamily of seven-helical receptors: The same and not the same. Sakmar, T.P. (2002) Curr. Opin. Cell Biol. 14: 189-195 Seven transmembrane-spanning receptors and heart function. Rockman et al., (2002) Nature 415:206-212 Akabas Lecture 10 9/22/08 Epithelial Physiology Intestinal ion transport and the pathophysiology of diarrhea. Field, M. (2003) JCI 111:931-943 Supplemental Reading Unraveling protein sorting. Nelson and Rodriguez-Boulan. (2004) Nature Cell Biol. 6:282-285 Toxigenic diarrheas, congenital diarrheas, and cystic fibrosis: Disorders of intestinal ion transport. Field, M. & Semrad, C.E. (1993) Annu. Rev. Physiol. 55:631-655 Akabas Review on 9/26/08 - Exam #1 Due on 10/03/08 Lecture 11 10/08/08 Skeletal Muscle Getting to Grips with Contraction: the Interplay of Structure and Biochemistry. Huxley (1998) TIBS 23:84-87 The Early History of the Biochemistry of Muscle Contraction. Szent-Gyorgyi A.G. (2004) J. Gen. Physiol. 123:631-641. The Sliding Filament Model 1972-2004. Cooke R. (2004) J. Gen. Physiol. 123:643-656. Myosin movie Supplemental Reading Muscle section in Molecular Cell Biology Sosa Lecture 12 10/17/08 Smooth Muscle Tardiff Lecture 13 10/24/08 Autonomic Nervous System and Hemodynamics Akabas Lecture 14 10/29/08 Cardiac Electrophysiology Molecular Biology of K+ channels and their role in cardiac arrhythmias Am. J. Med. 110:50-59 Optional Readings Molecular and cellular mechanisms of cardiac arrhythmias Cell 104:569-580 Supplemental Reading Commentary: The anatomy of an arrhythmia J. Clin. Invest. (2004) 113:662-664 A simulation study of the effects of cardiac anatomy in ventricular fibrillation J. Clin. Invest. (2004) 113:686-693 Akabas Lecture 15 10/31/08 Cardiac Pump Dynamics 1 Physiology by Berne and Levy, Chapter 23 and pages 387-397 Tardiff Lecture 16 11/3/08 Cardiac Pump Dynamics 2 Tardiff Lecture 17 11/5/08 Molecular Contractility and Length-dependent Activation Frank-Starling Relationship, Moss and Fitzsimmons (2002) Circ. Res. 90:11-13 Calcium, cross-bridges and the Frank-Starling Relationship, Fuchs and Smith (2001) News Physiol. Sci. 16:5-10 Myofilament calcium sensitivity in skinned rat cardiac trabeculae, Konhilas et al., (2002) Circ. Res. 90:59-65 Tardiff Lecture 18 11/7/08 Excitation-Contraction and Myocellular Energetics Cardiac excitation-contraction coupling, D.M. Bers, (2002) Nature 415:198-205 Failing energetics in failing hearts, Dzeja et al., (2000) Curr. Cardiol. Rpts. 2:212-217 Tardiff Lecture 19 11/10/08 The Neurohormonal Control of Cardiac Contractility Seven transmembrane-spanning receptors and heart function. Rockman et al., (2002) Nature 415:206-212 Tardiff Lecture 20 11/12/08 Myocellular Mechanotransduction The failing heart, Towbin and Bowles, (2002) Nature 415:227-233 Stress pathways and heart failure, K.R. Chien, (1999) Cell 98:555-558 Tardiff Lecture 21 11/14/08 Stem Cells and Cardiac Regeneration Lost in translation. (2004) Chien, K.R. Nature 428:607-8 Regenerating the heart. (2005) Laflamme, M.A. and Murry, C.E. Nature Biotechnol. 23:845-856 Supplemental Stem Cell Readings Hematopoetic stem cells do not transdifferentiate into .... (2004) Murry et al., Nature 428:664-669 Hematopoetic stem cells adopt mature haematopoetic fates in.... (2004) Balsam et al., Nature 428:668-674 Bone marrow cells regenerate infarcted myocardium. (2001) Orlic et al., Nature 410:701-706 Tardiff Review on 11/17/08 - Exam #2 Due on 11/21/08 Lecture 22 11/21/08 Glomerular Filtration #1 Structural determinants of glomerular permeability. Dean et al., (2001) Am. J. Physiol. 281:F579-F596 Proteinuria: is it all in the foot? (2007) J Clin Invest. 117:2079-2082 Signaling at the Slit Diaphragm. (2004) J Am Soc Nephrol. 15:1382-1391. NPHS2, encoding the glomerular protein podocin… (2000) Nature Genetics 24:349-354. Proteolytic processing of dynamin by cytoplasmic cathepsin L is a mechanism for proteinuric kidney disease. (2007) J Clin Invest. 117:2095-2104. Getting a foothold in nephrotic syndrome. Nature Genetics 24:333-335. Kaskel Lecture 23 11/24/08 Glomerular Filtration #2 Kaskel Lecture 24 12/1/08 Tubular Transport - Kidney Optional Readings Freshwater or Marine Origin of Vertebrates Barrtin is a Cl- channel beta subunit crucial for renal Cl- reabsorption Nature 414:558-562 (2001) Akabas Lecture 25 12/3/08 Body Response to Osmolarity Changes - Kidney Akabas Lecture 26 12/5/08 Regulation of Blood Volume Optional Readings Importance of quantitative genetic variations in the etiology of hypertension. Smithies et al., (2000) Kid. Int. 58:2265-2280 Akabas Lecture 27 12/9/08 Hormonal Regulation of Renal Tubular Transport Long term regulation of aquaporins in the kidney. (1999) Marples et al. Am. J. Physiol. Renal 45:F331-F339 Molecular biology of natriuretic peptides and nitric oxide synthases. (2001) Kone. Cardiovasc. Res. 51:429-441 Schuster Lecture 28 12/12/08 Hormonal Responses to Volume Changes Molecular mechanisms of hypertension. (2001) Lifton et al. Cell 104:545-566. Schuster Review on 12/18/08 - Exam #3 Due on 1/5/09 Lecture 29 1/5/09 O2 Needs / O2 Transport Proteins / O2 Sensors Akabas Lecture 30 1/7/09 Pulmonary Gas Exchange Optional Readings Fibulin-5 is an elastin binding protein... Yanagisawa et al., (2002) Nature 415:168-171 Akabas Lecture 31 1/9/09 Pulmonary Muscle Mechanisms; Neural Control of Respiration Caruana-Montaldo et al., (2000) The Control of Breathing in Clinical Practice. Chest 117:205-225 Optional Readings How Cells Endure Low Oxygen. Marx (2004) Science 303:1454-1456 Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression. Wenger, 2002 FASEB J. 11:1151-1162 Structure of factor inhibiting HIF. Dann et al. (2002) PNAS 99:15351-15356 Carbonic anhydrase: New insights from an ancient enzyme. Tripp et al. (2001) J. Biol. Chem. 276:48615-48618 New insights into the pathogenesis of asthma. Elias et al. (2003) JCI 111:291-297 Akabas Lecture 32 1/12/09 Buffers, Primary Acid-Base Disorders Schuster Lecture 33 1/14/09 Tubular Acid-Base Transport, Regulation Schuster Review on 1/16/09 - Exam #4 Due on 1/23/09

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