History

• Gordon C. Ring, Ph.D., was the first chair of the Department of Physiology. He focused the department on cardiovascular physiology and the noninvasive assessment of pulmonary function, leading a robust cardiovascular research and training program. Dr. Ring and colleagues used the electro kymograph to estimate pulmonary arterial pressure from arterial pulse wave velocity, allowing improved access to study pulmonary hypertension.
• Morris Rockstein, Ph.D., and Edward Chambers, M.D., brought state-of-the-art studies of cellular and molecular physiology to the department. They used model systems to reveal molecular mechanisms underlying physiological function.
  • Dr. Rockstein’s innovative research employed house flies to study aging and was a pioneer in the field of biogerontology, tracking changes in enzymes and nucleotides over time, including biochemical aging in the mammalian heart. In addition to his 20 years as a faculty member, Dr. Rockstein also served as chair from 1967 to 1971. Following Dr. Ring, Dr. Chambers gained international recognition for his study of fertilization using sea urchin eggs. His early studies examined the ionic requirements of fertilization, including the role of Ca²⁺, Na⁺, and proteolytic enzymes. His later studies used voltage-clamp techniques to characterize sperm-induced currents at fertilization and the stages leading to and following fusion of sperm and egg plasma membranes.

Werner Loewenstein, Ph.D., became department chair as the formal name expanded to the Department of Physiology and Biophysics. Dr. Loewenstein understood the immense power of applying physical principles toward resolving physiological function. His work contributed significantly to understanding mechanotransduction. He also investigated how communication through gap junctions can influence cancer growth.

Dr. Loewenstein established the Ph.D. program in cellular physiology and molecular biophysics, which was supported by an NIH T32 training grant for 35 years. Faculty research interests emphasized neuroscience, including:

• A quantitative description of short-term synaptic plasticity, including the discovery of the augmentation component of increased transmitter release, a description of interactions among the plasticity components, and development of a quantitative model that predicts the dynamic properties of release.
• Early demonstration of molecular motion associated with activation and inactivation of Na⁺ channels.
• The discovery and characterization of four ion channels at the single-channel level, including BK and SK.
• Development of novel approaches for single-channel analysis, including identification of kinetic states, transition pathways, and rate constants.
• Development of kinetic schemes to account for the Ca²⁺-activation of BK channels at the single-channel level.
• Identifying temperature-dependent energetic differences between evoked and spontaneous transmitter release.
• Providing the first demonstration of axonal chemotaxis toward a nerve growth factor.
• Purification of neurotrophic serum factor selenoprotein P.
• Developing the first in vitro proliferation of neuronal progenitor cells.
• Development of lipid-mediated transfer of mRNA into cultured cells to study gap junction control of myometrial contractions.
• Isolation of a genomic clone of connexin43 and demonstration of its transcriptional regulation by estrogen.
• Development of the paired oocyte assay to study gap junctions through protein expression, including the first demonstration of gap junction channel formation by the first cloned gap junction protein, Cx32.
• Demonstrating the electrophysiological contributions of individual synapses identified in the electron microscope to overall synaptic potentials recorded physiologically.
• Discovering that neurons which make fully functional connections with targets can be eliminated during development.
• Tracking microglia in living tissue and demonstrating they can rapidly move to nerve lesions.
• Discovering that CNS neurons contain a structurally distinct form of c-src protein that has activated tyrosylkinase activity.
• Discovering that astrocytes produce interferon and

Karl L. Magleby, Ph.D., was selected as chair, recognizing two decades of influential research and service. Dr. Magleby developed quantitative models to reveal the complex mechanisms underlying short-term synaptic plasticity and the gating of single ion channels. Dr. Magleby received the prestigious Kenneth Cole Award at the 2009 Biophysical Society Meeting for his contributions to membrane biophysics.

As chair, Dr. Magleby expanded the research interests of the department by recruiting faculty working in novel areas of sensory physiology and glial function.

Examples of research during the Magleby years include:

• Establishment of basic gap junction channel principles, including construction of rectifying gap junction channels and determination of the function of a voltage gate as a modifier of channel selectivity.
• Identification of Pannexin1 as a large-pore channel capable of releasing ATP to act as a signaling molecule.
• Establishing the role of Panx1 in physiological processes, including regulation of oxygen delivery and mucociliary clearance.
• Computer coding of self-directing algorithms to identify kinetic components of single-channel gating without the need to specify starting parameters.
• Demonstrating that presynaptic mitochondria buffer physiological Ca²⁺ loads and contribute to post-tetanic potentiation.
• Understanding the dynamic strengths of cell-adhesion molecules using single-molecule atomic force microscopy (AFM).
• Using force spectroscopy to reveal that the forced unbinding of leukocyte adhesion complexes overcomes multiple energy barriers, with a steep inner barrier conferring high mechanical strength.
• Characterizing the electrical properties of vertebrate axons, focusing on the sub-myelin region and contributions of K⁺ channels in the internodal region to action potential propagation.
• Performing studies of NADH and Ca²⁺ metabolism in neurons and nerve terminals, focusing on factors offering neuronal protection under stress.
• Demonstrating that reflection of action potentials at axon branches can be used by the nervous system to enhance synaptic transmission.
• Showing that transplanted neurons (retinal ganglion cells) can integrate into retinas of adult rats and respond to light.
• Discovering the highly complex, multistep process that guides microglial cells to neuronal lesions.
• Carrying out systematic studies of the molecular and cellular physiology underlying taste, including identification and function of the first mammalian taste receptor and its transduction pathways.
• Using single-cell RNA-seq to define molecular classes of sensory neurons, map their peripheral and central projections, and document their stimulus–response profiles.
• Using novel cellular biosensors to identify synaptic transmitters released by taste bud cells.
• Using intracellular calcium-sensing probes to develop new approaches for recording taste cell activity and discovering that important synaptic interactions occur between taste bud cells during gustatory activation, suggesting that taste buds are akin to miniature computers that perform limited information processing prior to transmitting signals to the brain.
• Developing sophisticated in vivo confocal calcium imaging procedures to study how trigeminal and geniculate ganglia receive and integrate oral sensory information.
• Discovering that neurons utilize caspase-3 (CPP32) as a principal effector in the apoptotic pathway following spinal cord injury, traumatic brain injury, and stroke.
• Demonstrating that neurons contain the NLRP1 inflammasome that initiates pyroptosis following spinal cord injury, traumatic brain injury, and stroke.
• Developing an anti-inflammatory drug, IC100, to treat inflammasome activation.
• Using in vivo studies in C. elegans as a model to uncover fundamental mechanisms by which glial cells regulate neuronal function and sensory perception.
• Finding that glia actively shape neural signaling through ion and solute transport, neurotransmitter release, and pH regulation, establishing glia as key determinants of sensory specificity and neural homeostasis.
• Developing molecular gating mechanisms of the channels underlying the IKs currents in heart; developing and testing PUFA analogs to determine their potential for the treatment of Long QT syndrome.
• Demonstrating that the gating of BK channels is consistent with a two-tiered allosteric mechanism that accounts for the simultaneous activation of BK channels by voltage and Ca²⁺ at the single-channel level.
• Applying physical approaches to describe conductance, selectivity, and gating of ion channels from basic physical principles to determine minimal models that account for these biological functions.
• Understanding the mechanisms of vesicle fusion and transmitter release and regulation, including development of biophysical methods to study fusion pores (analogous to single-channel recordings), real-time FRET imaging of SNAP25 incorporation indicating SNARE complex assembly/disassembly and vesicle priming in live cells, and molecular dynamics simulations of SNARE proteins in membranes, fusion-pore dynamics, and their complexes with other proteins.

In 2025, faculty member Nirupa Chaudhari, Ph.D., was awarded the Max Mozell Award for Outstanding Achievement in the Chemical Senses from the Association for Chemoreception Sciences.