Growth at Cold Temperature Increases the Number of Motor Neurons to Optimize Locomotor Function

Laura Borodinsky, Ph.D.Laura Borodinsky, Ph.D.

During vertebrate development spinal neurons acquire specialized identities and form a network that carries out sensorimotor functions. Intrinsic spontaneous electrical activity regulates different aspects of the birth and differentiation of spinal neurons. Whether environmental cues modulate electrical activity in developing spinal neurons and in turn influence their specialization and survival to generate the circuits underlying sensorimotor function remains unclear. Here we show that growing frog embryos at cold temperature results in swimming larvae with an increase in the number of spinal motor neurons compared to larvae raised in warm temperature. This change in spinal cord development optimizes the escape response to gentle touch of animals grown and tested at cold temperatures. The cold-sensitive channel TRPM8 increases Ca2+ spike frequency of developing ventral spinal neurons, which in turn regulates expression of the motor neuron master transcription factor HB9. TRPM8 is necessary for both the increase in motor neuron number of animals grown in cold temperatures and for their enhanced sensorimotor behavior when tested at cold temperatures. These findings suggest the environment modulates neuronal differentiation to optimize the behavioral outcome of the developing organism. Given that fetuses and preterm neonates lack mature thermoregulation, our findings suggest aberrant fluctuations in fetal or neonatal body temperature may impact neurodevelopment.

This new study from the Borodinsky lab, has been accepted and published in the journal Current Biology. Congratulations!!

Read the paper from here (PDF)

Read more about this study on UC Davis Medical School’s press release »

Tuning Cardiac EC-coupling during Fight or Flight

Rose Ellen Dixon, Ph.D.Rose Ellen Dixon, Ph.D.

New work from the Dixon lab revealing a new facet of β-adrenergic receptor (β -AR) mediated regulation of cardiac L-type calcium channels CaV1.2 appears in the current issue of The Journal of Physiology. The work demonstrates that stimulation of β-ARs with isoproterenol (ISO) induces a never before appreciated, rapid, dynamic increase in the expression and cooperative gating behavior of CaV1.2 channels in the sarcolemma of adult mouse ventricular myocytes. This striking response is PKA-dependent and manifests as the formation of CaV1.2 channel ‘super-clusters’ in response to ISO, in the t-tubule sarcolemma of these freshly isolated cells. Ito et al. demonstrate this with cutting-edge super-resolution imaging approaches in both fixed and live cells and study the functional implications with electrophysiology and Ca2+ imaging approaches. See this dynamic super-clustering occurring before your eyes in a particularly novel and exciting dataset recorded from live ventricular myocytes (view here). On the basis of these data, Ito et al. propose a revised model for β-AR-mediated regulation of CaV1.2 channels in the heart wherein a pre-synthesized pool of sub-sarcolemmal CaV1.2 channel- containing vesicles/endosomes resides in cardiomyocytes and can be mobilized to the sarcolemma to tune EC-coupling to meet metabolic and/or hemodynamic demands.

The article and accompanying ‘Perspectives’ commentary (written by William Louch) appears in the current issue of The Journal of Physiology.

Article:

β‐adrenergic‐mediated dynamic augmentation of sarcolemmal CaV1.2 clustering and co‐operativity in ventricular myocytes
Danica W. Ito, Karen I. Hannigan, Debapriya Ghosh, Bing Xu, Silvia G. Del Villar, Yang K. Xiang, Eamonn J. Dickson, Manuel F. Navedo, and Rose E. Dixon

Perspective:

Channel surfing: new insights into plasticity of excitation‐contraction coupling
William E. Louch

2018 Dean's Team Award for Excellence in Research

Colleen Clancy, Ph.D.Colleen Clancy, Ph.D.

Luis Fernando Santana, Ph.D.Luis Fernando Santana, Ph.D.

Igor Vorobyov, Ph.D.Igor Vorobyov, Ph.D.

Congratulations to Dr. Colleen Clancy's SPARC team that includes Dr. Luis F. Santana, Professor and Chair, and Dr. Igor Vorobyov, Assistant Professor, to have been selected as a recipient of the 2018 Dean's Team Award for Excellence. Their team is being recognized for outstanding multi-disciplinary team contributions in the area of Research. Congratulations!!

Atomic-scale Simulation of Antiarrhythmic Drug Interaction with Cardiac Cells

Vladimir Yarov-Yarovoy, Colleen Clancy, Phuong Tran Nguyen, Igor Vorobyov and Kevin DeMarco Left to right: Vladimir Yarov-Yarovoy, Colleen Clancy, Phuong Tran Nguyen, Igor Vorobyov and Kevin DeMarco

To unravel the mysterious mechanisms of drug potency for the treatment of cardiac arrhythmias, a group of researchers at UC Davis have developed novel simulations that provide insights on vital atomic-scale drug-cardiac cells interactions. These simulations, published today in PNAS (Proceedings of the National Academy of Sciences), may lead the way to better development of new antiarrhythmic drugs targeting voltage-gated sodium (NaV) channels, specialized protein molecules in the cardiac cell membrane.

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2018-2019 Chancellor's Achievement Award for Diversity and Community

Colleen Clancy, Ph.D.Colleen Clancy, Ph.D.

Collen Clancy, Ph.D., Associate Vice Chancellor for Academic Personnel and a Professor in the Department of Physiology and Membrane Biology, was this year’s recipient of the Chancellor’s Achievement Award for Diversity and community for her commitment and outstanding work to enhance diversity in UC Davis. Congratulations!!

Voltage Sensors Detained by Tarantula Venom

Jon Sack, Ph.D. Jon Sack, Ph.D.

The Sack laboratory has published an article in the Journal of General Physiology determining the statistical thermodynamics underpinning the mechanism by which an especially powerful tarantula toxin prevents an ion channel from opening. They found that the sneaky spider toxin finds unsuspecting channels that are patiently resting, and binds to them such that they their voltage sensors can’t respond to physiological voltage changes anymore. The ion channels the toxin inhibits are important for a host of physiological functions including neuronal signaling, muscle contraction, and insulin secretion. This study of the toxin revealed new aspects of how the ion channels they bind work. Additionally, understanding precisely how the toxin works allows the many researchers who use this toxin for physiological research to understand what the toxin is actually doing to ion channels. This research also revealed new uses of the toxin: it can be used not just to block ion channel currents, but to immobilize their voltage sensors as well. This work was featured in a wonderfully thorough commentary in the Journal, which unpacks the physics and the relevance of the Sack laboratory’s findings.

The article and commentary are soon to be included in a special Journal of General Physiology issue, Molecular Physiology of the Cell Membrane: An Integrative Perspective from Experiment and Computation.

Article:

The tarantula toxin GxTx detains K+ channel gating charges in their resting conformation

Drew C. Tilley, Juan M. Angueyra, Kenneth S. Eum, Heesoo Kim, Luke H. Chao, Anthony W. Peng, Jon T. Sack

The Journal of General Physiology DOI: 10.1085/jgp.201812213

Commentary:

Unlocking the gating mechanism of Kv2.1 using guangxitoxin

Marco A. Navarro, Lorin S. Milescu, Mirela Milescu

The Journal of General Physiology DOI: 10.1085/jgp.201812254

Digitizing interactions between the brain and the heart

Colleen Clancy, Ph.D.Colleen Clancy, Ph.D.

Luis Fernando Santana, Ph.D.Luis Fernando Santana, Ph.D.

UC Davis Health researchers have been awarded $5.2 million over four years from the National Institutes of Health to develop the first computerized model of the relationship between the nervous system and cardiovascular disease.

The tool is expected to lead to new understanding of conditions such as hypertension, arrhythmia, heart failure and stroke, along with how those conditions change in response to treatment.

“We know that imbalance between the nervous and cardiovascular systems contributes to heart disease, however we don’t fully understand how,” said principal investigator Colleen Clancy, professor of physiology and membrane biology. “Our new suite of tools will showcase those interactions in a real-time, visual way and could lead to new interventions for preventing and even reversing heart disease.”

Co-principal investigators on the grant are Eleonora Grandi, associate professor of pharmacology, and L. Fernando Santana, professor and chair of physiology and membrane biology.

Read more about this news article here »

Dr. Colleen Clancy lauds UC Davis faculty diversity in overseas presentation

Colleen Clancy, Ph.D.Colleen Clancy, Ph.D.

When administrators at the University of Zurich sought a guest speaker to discuss promoting women in faculty roles in medicine, they tapped a UC Davis Health leader who has become a prominent voice on the subject.

Colleen E. Clancy, associate vice chancellor for academic personnel and a professor in the Department of Physiology and Membrane Biology and Department of Pharmacology, traveled to Switzerland in mid-September to deliver a talk titled, “Advancing women and other underrepresented groups in medicine: Lessons and successes at the University of California.”

Read more about this news article here »

Advancing Diabetes Research: Mark Huising Receives Faculty Research Award

Mark Huising, Ph.D.Mark Huising, Ph.D.

Science is about advancing knowledge, work that requires dedication and tenacity. Another component is a keen and critical eye, as discovery is predicated on synthesizing and evaluating the work that came before.

For his discovery of a new type of insulin-producing cell, among other research contributions featured in the journal Cell Metabolism, Associate Professor Mark Huising, Department of Physiology and Department of Neurobiology, Physiology and Behavior, was awarded the 2017-2018 College of Biological Sciences Faculty Research Award.

Read more about this news article here »

Jon Horvath, graduate student from Eamonn Dickson's lab earns academic All-America honor

Jon HorvathJon Horvath

Jon Horvath, graduate student from Eamonn Dickson's lab makes the 2017-2018 Google Cloud Academic All-America Division I Cross Country/Track and Field Team with first-team status, as announced by the College Sports Information Directors of America (CoSIDA) on Thursday afternoon.

Horvath, a neurobiology, physiology, and behavior major with a perfect 4.0 GPA, has become the second cross-country runner in the past five years to make the first-team list. The first of the two was UC Davis alumni Trevor Halsted, who received this honor in both the 2014 and 2015 seasons.

University Medalist Emily Eijansantos Learned Value of Perseverance in Lab

Emily Eijansantos from Dr. Aldrin Gomes's labDr. Aldrin Gomes, Emily Eijansantos

Emily Eijansantos, a graduating senior from Dr. Aldrin Gomes's lab, recently received the University Medal, UC Davis' top graduating senior award. In Dr. Gomes's lab, she studied the effects of ibuprofen on heart cells and the immunoproteasome.

Read more about this news article here »

A study from the Borodinsky lab is highlighted in the Journal of Neuroscience

JNeurosci-BorodinskyClick to enlarge

The brain and spinal cord begin as a group of cells in the embryo that folds in on itself to form the neural tube. Some of the most common birth defects, such as spina bifida, are caused by a neural tube that fails to close completely. Against the prevailing view that the side effects of antiepileptic (AED) drugs contribute to the prevalence of neural tube defects among children of epileptic mothers, a study led by a former postdoctoral fellow, Eduardo Sequerra and a current UC Davis graduate student, Raman Goyal, from Dr. Laura Borodinsky's lab discovers that in frog embryos the neurotransmitter glutamate and N-methyl-aspartate (NMDA) receptors play an important part in the proliferation and migration of the cells that form the neural tube, which were compromised in embryos treated with the widely-used AED valproic acid and led to neural tube defects. Understanding the mechanisms of neurotransmitter signaling during neural tube formation may contribute to identifying and developing antiepileptic drugs that are safer during pregnancy.

Read more about this news article here »

Marijuana: Clearing the smoke

Yu-Fung Lin, Ph.D.Yu-Fung Lin, Ph.D.

Dr. Yu-Fung Lin’s “Physiology of Cannabis” (HPH 115) course was highlighted in a segment of the CBS Sunday Morning Show about medicinal and recreational cannabis use.

Watch the show here »

American Physiological Society (APS) Fellow

Martha E. O'Donnell, Ph.D.Martha E. O'Donnell, Ph.D.

Departmental faculty member Martha E. O'Donnell, Ph.D. has been approved as a Fellow of the American Physiological Society. The rank of Fellow is designed to honor distinguished members who have demonstrated excellence in science, contributed to the physiological sciences and served the Society. Fellows are considered to be in the top tier of all eligible members. Congratulations!!

TRPV4 in the battle of the sexes

Luis Fernando Santana, Ph.D.Luis Fernando Santana, Ph.D.

The recent paper by the departmental chair and faculty member Luis Fernando Santana, Ph.D., along with Sendoa Tajada, Ph.D., a researcher from his lab, has been accepted for publication in the Journal of General Physiology.

This article has been recommended in F1000Prime as being of special significance in its field by F1000 Faculty Member Mark Dell’Acqua. Read more about this recommendation from here »

Abstract: New JGP paper explains sexual dimorphism and tissue-specific activity of TRPV4.

The broadly expressed transient receptor potential vanilloid 4 (TRPV4) calcium channel allows an enormous amount of calcium into the cell (up to 100-fold greater calcium flux than those produced by voltage-gated Cav1.2 calcium channels; 1). In vascular smooth muscle, TRPV4 channels help regulate vascular tone. In this month’s JGP, Tajada et al. provide surprising new insights about how TRPV4 activity is regulated.

Read more about this paper here »

Structural Insights into the Atomistic Mechanisms of Action of Small Molecule Inhibitors Targeting the KCa3.1 Channel Pore

Vladimir Yarov-Yarovoy, Ph.D.Vladimir Yarov-Yarovoy, Ph.D.

The recent paper by the department faculty member, Vladimir Yarov-Yarovoy, Ph.D., has been featured on the cover of April 2017 issue of Molecular Pharmacology.

Read more about this paper at the following links:
http://molpharm.aspetjournals.org/content/91/4/392
http://molpharm.aspetjournals.org/content/91/4.cover-expansion

Undergraduate course on the 'Physiology of Cannabis' offered this spring at UC Davis

Physiology of Cannabis

A new undergraduate course on “Physiology of Cannabis” (HPH 115) will be offered at UC Davis this spring to raise awareness and understanding of how cannabis and cannabinoids affect the body.

Read more on The Davis Enterprise.

Dr. Aldrin Gomes, named 2017 Chancellor's Fellow

Aldrin Gomes, Ph.D.Aldrin Gomes, Ph.D.

Dr. Aldrin Gomes, was among the Chancellor's Fellows named this year. This year’s class of Chancellor’s Fellows comprises 11 associate professors or recently promoted full professors — rising stars in their fields who have now received one of the university’s highest honors and will retain the title for five years.

Read more about this news article here »

Are gelatin supplements good for your joints?

Keith Baar, Ph.D.Keith Baar, Ph.D.

A new study suggests that consuming a gelatin supplement, plus a burst of intensive exercise, can help build ligaments, tendons and bones.

The study, from departmental faculty member Keith Baar, Ph.D. and his Functional Molecular Biology Laboratory, is published in the January issue of the American Journal of Clinical Nutrition.

Read more about this news article here »

UC Davis Joins National Effort on Links Between Health and Exercise

Keith Baar, Ph.D.Keith Baar, Ph.D.

The National Institutes of Health announced a six-year, $170 million nationwide project to dig deep into the molecular changes that come from physical activity, and how they influence health. Departmental faculty member, Keith Baar, Ph.D., is taking part in the effort.

Read more on UC Davis News page and SacBee.

2016-2017 Chancellor's Fellow

Aldrin Gomes, Ph.D.Aldrin Gomes, Ph.D.

Departmental faculty member Aldrin Gomes, Ph.D., has been selected as 2016-2017 Chancellor's Fellow. The Chancellor's Fellows Program was established in 2000 to honor the achievements of outstanding faculty members for the quality and significance of their research and teaching.

Ca2+ entry into neurons is facilitated by cooperative gating of clustered CaV1.3 channels

Luis Fernando Santana, Ph.D.Luis Fernando Santana, Ph.D.

Voltage-gated calcium channels open in unison, rather than independently, to allow calcium ions into and activate excitable cells such as neurons and muscle cells, departmental chair and faculty member Luis Fernando Santana, Ph.D., along with researchers from his lab and the researchers from the University of Washington have found.

The research defies earlier electrophysiology canon and undermines the previously held belief that calcium channels function independently. The study is published online in the journal eLIFE.

Peppers a hot topic in medical research at UC Davis

capsaicin-molecule

Humans love Sriracha sauce, and the pleasurable, painful sensation that makes us want to slather tacos, rice and barbecue with it and other spicy condiments comes down to one molecule: capsaicin. Departmental faculty members Jie Zheng, Ph.D. and Vladimir Yarov-Yarovoy, Ph.D., in collaboration with researchers in China, recently got an unprecedented, close-up view of this molecule, as well as what happens inside our bodies when we eat the spicy foods that contain it. Read more about this article here »

Structural mechanism underlying capsaicin binding and activation of the TRPV1 ion channel

thermoTRPs-as-T-sensors

Departmental faculty member Jie Zheng, along with researchers from his lab, have identified the molecular interactions that allow capsaicin to activate the body’s primary receptor for sensing heat and pain, paving the way for the design of more selective and effective drugs to relieve pain. Their study appeared online June 8, 2015 in the journal, Nature Chemical Biology.

A foreign member of the Norwegian Academy of Science and Letters

Fitz-Roy Curry, Ph.D.Fitz-Roy Curry, Ph.D.

Departmental faculty member Fitz-Roy Curry, Ph.D., was elected as a foreign member of the Norwegian Academy of Science and Letters in March, 2015. Dr. Curry was introduced into the Academy on May 4, 2015 at the annual meeting in Oslo. He joins the Medical Sciences Group in the Division of Natural Sciences, which has 12 other foreign members worldwide. Dr. Curry is recognized for his research on the microcirculation, particularly the mechanisms that regulate exchange of substances between circulating blood and the body tissues. His recent work has focused on recovery of normal function after exposure to inflammatory conditions. Dr. Curry has had an active collaboration with faculty and research fellows from the Department of Biomedicine at the University of Bergen, Norway since 2005. Further details of the Norwegian Academy of Science and Letters can be found at http://english.dnva.no/.

Nishimaru-Tsuchiya International Award

Dr. Curry will receive the Nishimaru-Tsuchiya Award during the 10th World Congress for Microcirculation in Kyoto, Japan September 25-27, 2015. The World Congress is held every 4-5 years. There have been 6 Awards since 1984. On the occasion of the World Congress for Microcirculation, this important award is given by the Japanese Society for Microcirculation to researchers in any country with outstanding achievements in the field of microcirculation research, who have thereby greatly contributed to the development of the Japanese Society for Microcirculation. Further details of this award can be found  at http://www.jsmicrocirc.com/english.html.

AAAs Lifetime Mentor Award

Barbara Horwitz, Ph.D.Barbara Horwitz, Ph.D.

Departmental faculty member Barbara Horwitz, Ph.D. was honored with AAAs Lifetime Mentor Award for making significant contributions towards increasing diversity in Physiology.

Read more about this news article here »

Tarantula venom illuminates electrical activity in live cells

Sack and Yarov-Yarovoy Labs(from left to right) Vladimir Yarov-Yarovoy, Daniel Austin, Sebastian Fletcher-Taylor, Jon Sack and Kenneth S. Eum, who passed away earlier this year. The team has dedicated the work to his memory. "Ken was a talented postdoctoral student, a driven and caring soul who brought joy to the lives of those who knew him," they said.

Researchers from Sack and Yarov-Yarovoy labs, Lawrence Berkeley National Laboratory and Marine Biological Laboratory in Woods Hole, Massachusetts, have created a cellular probe that combines a tarantula toxin with a fluorescent compound to help scientists observe electrical activity in neurons and other cells. The probe binds to a voltage-activated potassium ion channel subtype, lighting up when the channel is turned off and dimming when it is activated. 

This is the first time researchers have been able to visually observe these electrical signaling proteins turn on without genetic modification. These visualization tools are prototypes of probes that could some day help researchers better understand the ion channel dysfunctions that lead to epilepsy, cardiac arrhythmias and other conditions. The study appears in the Proceedings of the National Academy of Sciences (PNAS) on October 20.

Read more about this news article here »

Chancellor honors 7 for achievement in diversity and community

Barbara Horwitz, Ph.D.Barbara Horwitz, Ph.D.

Departmental faculty member Barbara Horwitz, Ph.D. is a recipient of The 2014 Chancellor's Achievement Awards for Diversity and Community in the category of Academic Senate.

Read more about this news article here »