Department of Physiology

Chairman Benjamin Kaminer

Programs of Study

Graduate studies in the Department of Physiology provide the student with oppor-tunities to be trained in interdisciplinary approaches in molecular and cellular physiology. The major areas being addressed and the technologies being employed by the faculty are as follows:

Calcium regulation of molecular and cellular processes is investigated by using a variety of experimental techniques such as electrical recording of single channels, optical imaging, and x-ray diffraction. Calcium regulation is being approached through studies of the endoplasmic reticulum, an intracellular communication network which both sequesters and releases calcium, of cytoplasmic calcium-binding modulator proteins, of proteins binding phospholipids in membranes, and of regulatory proteins in muscle thin filaments and in epithelial cilia and sperm flagella. Physiological mechanisms are being elucidated in a variety of cell types through studies on the excitation-secretion coupling process in adrenal cells, on the excitation and adaptation of photoreceptors, and on the modulation of ion channel behavior and second messenger responses. Precise spatial and temporal measurements of calcium levels in single nerve and adrenal cells are being carried out by optical imaging, using both fluorescent probes and the genetically engineered photoprotein aequorin, and also with calcium-sensitive microelectrodes.

Another major emphasis concerns visual transduction mechanisms, combining electrophysiology, microspectrophotometric, and imaging technologies. The photochemistry of light and dark adaptation of vertebrate rods and cones is being approached from the viewpoint of intracellular second messengers and their modulation of ion channel function. The molecular basis for color vision is being explored through microspectrophotometric analysis of the characteristic pigments of single vertebrate photoreceptors and also through biophysical studies of isolated retinal pigments and reconstituted membranes, using a variety of spectroscopic methods. At an integrative level, neuron-glial interactions, peptidergic neurons, and comparative phototransduction mechanisms are being studied in several systems.

Membrane transport and ion channel studies focus on the application of nonequilibrium thermodynamics to ion channel function and reaction-diffusion systems, approached from a theoretical viewpoint, while other studies deal with the expression of ionic channels in developing cochlear neurons and their regulation by growth factors such as neurotrophins.

Structural biological research, combining biochemical, electron microscopic, and x-ray diffraction approaches, is aimed at understanding diverse physiological processes at the angstrom level. The organization of Z-band proteins in muscle is being established by monoclonal antibody localization to determine assembly mechanisms for myofibrillar proteins in normal muscles and in mutants with abnormal myofibrils. The specific arrangement of calcium regulatory proteins on skeletal and smooth muscle thin filaments is being elucidated by 3-dimensional image reconstruction to compare regulation in different muscle types. The structure of the annexins (a class of calcium-dependent phospholipid membrane binding proteins) and the structures of a variety of ligand binding proteins, protein-peptide complexes (such as calmodulin-target peptides) and enzymes (such as ornithine transcarbamylase and acetoacetate decarboxylase) are being determined by X-ray crystallography to identify the molecular modifications related to changes in physiological states.

Molecular biological techniques are being used to better understand the functions of physiologically relevant proteins. Examples are the cloning, sequencing, and expression of a calcium storage protein from the endoplasmic reticulum, the cloning and expression of Z-band proteins in Drosophila mutants, the differential expression and regulation of tubulin and microtubule-associated protein genes during ciliogenesis, the expression of mRNAs for various ion channels and rhodopsin in frog oocytes, and the bacterial expression of mammalian structural proteins, calcium regulatory proteins, and a number of enzymes.

Additional strengths are represented by faculty with joint appointments in other departments. These areas include: the physical properties of biopolymers; vitamin D function and metabolism; glucose transport and insulin action; cardiac function and the control of coronary vessels and erectile tissue; renal function; and respiratory system mechanics and modeling.

The department has a flexible program that takes into account the background and special interests of individual students. Typical coursework in the first year consists of two semesters each of human physiology, experimental methods in physiology, and biochemistry. In the second year, one semester courses in cell biology, cell physiology, biostatistics, and various electives are taken. Students also register for one semester of Physiology Seminar each year. During this time, MA students fulfill 3 months of laboratory research while PhD students fulfill 6 months, each consisting of 6-8 week rotations. MA students complete their requirements with either a thesis or a comprehensive exam. PhD students take a qualifying exam at the end of the second year, at which point an advisory committee is appointed to aid the student in outlining a thesis project and to monitor the student's progress. Upon satisfactory completion of the project, a thesis is submitted to the committee and a final oral examination is held.

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Courses

GMS PH 543 Human Physiology B
Prereq: consent of instructor. See MED ME 542 Human Physiology I. O'Bryan. 4 cr, 2nd sem.

GMS PH 740 Physiology
Lectures cover functional activity of various organ systems, excepting endocrine and central nervous systems. Emphasis on regulatory homeostatic mechanisms. Selected laboratory exercises as introduction to experimental approach for study of physiological mechanisms. O'Bryan, staff. 6 cr, 2nd sem.

GMS PH 741 Experimental Methods in Physiology A
Prereq: MED ME 751 and consent of instructor. Current research methods in cellular and molecular physiology, as applied to the study of macromolecular function, motility, ligand binding phenomena, and membrane function. Develops problem-solving skills and awareness of current approaches to research problems. Stephens, staff. 2 cr, 1st sem.

GMS PH 742 Experimental Methods in Physiology B
Prereq: consent of instructor. A practical approach to electrophysiology techniques. Garcia-Diaz, staff. 2 cr, 2nd sem.

GMS PH 745, 746 Special Topics in Physiology
Prereq: consent of instructor. Current and classical papers in a given area of physiology are assigned for reading and later discussion with students. Topics include mechanics of muscle, cell motility, membrane transport, sensory physiology, and instrumentation in physiological research. Variable cr, 1st & 2nd sem.

GMS PH 841, 842 Physiology Seminar
Students present seminars on their research and/or review literature related to their research. Students attend the seminars presented by staff and other students. Levy, staff. 2 cr each, 1st & 2nd sem.

GMS PH 843, 844 Cellular Physiology I and II
Prereq: consent of instructor. Lectures and discussion on: (1) membrane transport, thermodynamic and kinetic analysis; (2) electrophysiology of cell membranes, excitable membrane properties, electrical coupling, synaptic transmission; and (3) cell motility, molecular mechanism, and regulation of contraction of muscle and other cells; mechanisms of transduction of photoreceptors. Garcia-Diaz, staff. 4 cr, 1st & 2nd sem.

GMS MI 941, 942 Research Physiology
Variable cr

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Faculty

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