The National Institutes of Health (NIH) recently awarded Jonathan H. Jaggar, PhD, Maury Bronstein Endowed Professor in the Department of Physiology at the University of Tennessee Health Science Center (UTHSC), a $1,520,000 grant for his project titled “Blood Pressure Regulation by Smooth Muscle Cell Ion Channels.” The proposal is designed to study proteins called ion channels that regulate blood pressure and flow in the body.
Arteries contain smooth muscle cells, which regulate systemic blood pressure and blood flow within organs. Smooth muscle cells express several different ion channel proteins that regulate contractility, but physiological systemic blood pressure regulation by many of these proteins is unclear. Similarly, involvement of these proteins during high blood pressure (hypertension) is also poorly understood. A channel termed Transient Receptor Potential Polycystic (TRPP1) is present in arterial smooth muscle cells, but blood pressure regulation by this protein, signaling mechanisms involved, and the concept that targeting these proteins alleviates hypertension have not been studied. Dr. Jaggar will investigate the physiological and pathological significance of arterial smooth muscle cell TRPP1 channels to better understand blood pressure regulation and the potential to treat hypertension.
“Human mutations in TRPP1 lead to polycystic kidney disease, which is a disorder also associated with hypertension,” Dr. Jaggar said. “What has not been well studied are functions of TRPP1 in cell types outside of the kidney. The focus here is to investigate the regulation of blood pressure by TRPP1 channels in arterial smooth muscle cells.”
Currently, pharmacological modulators of TRPP1 channels do not exist. Therefore, in the aims of Dr. Jaggar’s new grant, they will study the concepts that genetic targeting of these proteins specifically in smooth muscle cells alters their function, modifies blood pressure, and discover whether targeting alleviates hypertension.
“The study of ion channel trafficking in the vasculature is a field of research unique to my lab,” said Dr. Jaggar. “Therefore, one of our aims will investigate how TRPP1 channels move around, or ‘traffic’ within arterial smooth muscle cells. What’s interesting about this specific ion channel is that the regulation of trafficking is very important to how it works physiologically.”
A better understanding of these ion channel functions plays a fundamental role in the development of novel therapies. The project is slated to be worked on through 2021.