News and Events
L-type channel inactivation balances the increased peak calcium current due to absence of Rad in cardiomyocytes
Ahern BM, Sebastian A, Levitan BM, Goh J, Andres DA, Satin J. L-type channel inactivation balances the increased peak calcium current due to absence of Rad in cardiomyocytes. J Gen Physiol. 2021 Sep 6;153(9):e202012854. doi: 10.1085/jgp.202012854.
The L-type Ca2+ channel (LTCC) provides trigger calcium to initiate cardiac contraction in a graded fashion that is regulated by L-type calcium current (ICa,L) amplitude and kinetics. Inactivation of LTCC is controlled to fine-tune calcium flux and is governed by voltage-dependent inactivation (VDI) and calcium-dependent inactivation (CDI). Rad is a monomeric G protein that regulates ICa,L and has recently been shown to be critical to β-adrenergic receptor (β-AR) modulation of ICa,L. Our previous work showed that cardiomyocyte-specific Rad knockout (cRadKO) resulted in elevated systolic function, underpinned by an increase in peak ICa,L, but without pathological remodeling.
What they did: Here, we sought to test whether Rad-depleted LTCC contributes to the fight-or-flight response independently of β-AR function, resulting in ICa,L kinetic modifications to homeostatically balance cardiomyocyte function. We recorded whole-cell ICa,L from ventricular cardiomyocytes from inducible cRadKO and control (CTRL) mice. The kinetics of ICa,L stimulated with isoproterenol in CTRL cardiomyocytes were indistinguishable from those of unstimulated cRadKO cardiomyocytes. CDI and VDI are both enhanced in cRadKO cardiomyocytes without differences in action potential duration or QT interval.To confirm that Rad loss modulates LTCC independently of β-AR stimulation, we crossed a β1,β2-AR double-knockout mouse with cRadKO, resulting in a Rad-inducible triple-knockout mouse.
What they found: Deletion of Rad in cardiomyocytes that do not express β1,β2-AR still yielded modulated ICa,L and elevated basal heart function. Thus, in the absence of Rad, increased Ca2+ influx is homeostatically balanced by accelerated CDI and VDI.
Why it matters: Our results indicate that the absence of Rad can modulate the LTCC without contribution of β1,β2-AR signaling and that Rad deletion supersedes β-AR signaling to the LTCC to enhance in vivo heart function.
What You Should Know About the Delta Variant
By: Becky Dutch, PhD, Vince Venditto, PhD, Ashley Montgomery-Yates, MD and Aaron Grubbs, MD
As the SARS-CoV-2 delta variant continues to spread across the United States and hospitals’ COVID-positive intake numbers climb again, many questions remain around both vaccine effectiveness and vaccination rates, and what these numbers could mean moving into the fall.
When viruses replicate, they make billions and billions of copies of themselves. Every time they make a copy, they can make mistakes. Over time, you will expect that normal viral evolution means you are going to start picking up variants. The delta variant is the first notable variant we’ve seen from COVID-19. It is beginning to spread rapidly in the United States because of the large population of unvaccinated people here.
While this is a scary notion, there is good news that comes from this information. We now have on good authority that the COVID-19 vaccine is doing what it was made to do. Most people who have been hospitalized recently for COVID-19 are not vaccinated. This is evidence that the vaccines are working. They are inducing the appropriate immune response to keep us protected, keep us out of the hospital and prevent death.
Some are expecting to see a surge in hospitalization rates coming in the fall. The issue is not that the delta variant is a more aggressive virus, it is just more transmissible, which makes it easier to catch. Last year, even the people who were not necessarily full believers in what the Centers for Disease Control and Prevention (CDC) was saying, had things in place that kept them safe in ways they did not even realize. Without the mandates we were previously under — masking, no mass gatherings and businesses shut down — health care workers fear that the variant will cause surges.
The discussion is once again going back to precautions we can take to keep each other safe. Vaccinated people have had a taste of no mask life, but is that really what we should be doing?
There is evidence that suggests a vaccinated person can get the delta variant. However, those who have gotten it have had a mild infection. Even if you are vaccinated, if you are attending mass gatherings, or have someone in your immediate circle who is immunocompromised, the best solution is to wear a mask. If we’ve learned anything from COVID-19, it is much better to err on the side of precaution when dealing with your health. And if you haven’t yet, get your COVID-19 vaccine!
Call for Applications: Pilot Funding
The UK Center for Clinical and Translational Science is now accepting applications for pilot projects. The purpose of this funding mechanism is to provide a new opportunity and resources to support innovative, collaborative research relevant to the health challenges and disparities faced by the nation and the citizens of Kentucky.
Grants are available in three categories:
EARLY CAREER INVESTIGATOR PILOT AWARD
This award is intended to support pilot studies by early stage investigators (see NIH definition in the RFA) to obtain preliminary data for an extramural grant submission. The maximum award will be $25,000 which must be spent over 12 months. This award is only open to investigators in the early stage of their career, or investigators who are transitioning into a new area. Applicants must identify a mentor to assist with the investigator’s training.
INNOVATION AND HIGH IMPACT PILOT AWARD
This award is for investigators at all stages of career development (early career, midlevel, and senior investigators) and is intended to stimulate innovation and to support pilot studies that will lead to extramural funding. The total award is limited to $50,000 which must be spent over 12 months.
See: https://www.ccts.uky.edu/media/2207 for more information on the above awards.
UK ALLIANCE RESEARCH PILOT AWARD
This award is for investigators at all stages of career development (early career, midlevel, and senior investigators) and is intended to support high impact-like projects that align with the mission of the ADORE (diabetes/obesity), K-RALD (lung disease) or the SPORE (GI cancer) Alliances. There will be three separate co-funded awards, one per alliance limited to $50,000 which must be spent over 12 months. Information for each Alliance can be found at https://med.uky.edu/alliance.
LOI due August 16 by 5pm
Notice of Meritorious LOI: September 3
Full Application due October 4
Funding Decisions: November 1
TISA Implementation Science Visiting Professor Series
Emerging Directions in Designing and Evaluating Implementation Strategies.
Date: Sep 8 2021 - 1:00pm to 2:30pm
Seminar Speaker: Byron Powell, PhD
Click here to register.
The University of Kentucky's Alliance Initiative capitalizes on collaboration and the transdisciplinary strategy built from the best practices and metrics across the nation in developing programmatic research. It is designed to provide seed funding and support for multidisciplinary teams of scientists, from colleges and centers across the University’s campus, to find answers to the health challenges that disproportionately affect Kentuckians. The CV-RPA is part of four Alliance Initiatives. Follow the Alliance Research Initiatives here.
PI: Julie Pendergast
Title: CAREER: Deciphering the Neural Network Orchestrating Sex Differences in Metabolic Circadian Rhythms
Sponsor: National Science Foundation
PI: Ann Stowe
Title: Rethinking Repair: Long-Term Adaptive Immunity Supports Functional Recovery for Stroke Patients
Sponsor: American Heart Association
The Gill Recognition Program!
Congratulations to Ken Campbell, PhD, Professor in Physiology, for receiving the May 2021 Gill Recognition Award. Ken was nominated by Mindy Thompson, Research Program Manager, Physiology.
"Dr. Campbell meets most, if not all, of the criteria for this award. A few years after his arrival at the University of Kentucky, Dr. Campbell developed an innovative approach with one of the cardiologist to startup a cardiac biobank using limited resources available to his lab. Dr. Campbell serves as the Director of Graduate Studies and teaches several courses to include MD826. He takes pride in making course material exciting, easily accessible and comprehendible. While most professors might dread receiving class reviews at the end of the semester, Dr. Campbell welcomes the opportunity for improvement. He frequently seeks ways to improve both professionally and personally. Dr. Campbell has an inspiring personality that allows him to encourage others and has allowed him to build an unbelievable internal and external network. The support he offers his colleagues and mentees is unsurpassed. This, I was able to witness when he had a lab reunion Zoom. Several of his previous students or post docs joined a Zoom reunion to catch up. All five of them had nothing but positive things to say about Dr. Campbell but most importantly, the work culture they described is the same, if not better, today. A positive work culture can be challenging to create let alone maintain, and improve, over the course of 17 years which speaks volumes to his character and leadership!"- Mindy Thompson
To read more about the Gill Recognition Awards see here (please note the website is being updated and may not include all recent winners).