Michael L. Jennings, Ph.D.

Michael L. Jennings

Professor and Chair
Ph.D., Harvard University
Office: (501) 296-1438
Lab: (501) 296-1439
JenningsMichaelL@uams.edu

My research is focused on the structure, function, and regulation of ion transport proteins. For many years we used the red blood cell chloride-bicarbonate exchange protein known as AE1 as a model system for studying coupled ion transport.  Recently our interest shifted to a protein known as BTR1 that is related to AE1.  Mutations in BTR1 cause a human condition called CHED (congenital hereditary endothelial dystrophy) of the cornea, which results in cloudy vision.  BTR1 has been reported to be a boron transporter, but we have found no evidence that it transports boron.  Instead it acts as a pH-regulated channel for H+/OH.  This project is a collaboration with Mark D. Parker of the University of Buffalo.

Another current interest is in hydrogen sulfide (H2S) and sulfide ion (HS) transport.   Although there is considerable evidence for the importance of H2S as a signaling molecule, until recently there were no measurements of H2S or HS transport through a mammalian cell membrane.  I measured the rates of dissipation of pH gradients across the human red blood cell membrane and found that these rates are strongly accelerated by low concentrations of H2S/HS.  With the help of some mathematical modeling, the pH transients were used to quantify the permeability of both H2S and HS.  Sulfide ion is transported rapidly by the Cl transporter AE1 (about 1/3 as rapidly as Cl), and H2S penetrates the membrane rapidly by either diffusing through the bilayer or through an aquaporin.  These measurements represent the first estimates of the permeation rates of H2S or HS across a mammalian cell membrane.

A new project is a collaboration with Haibo Zhao of the UAMS Department of Internal Medicine on a project designed to determine the role of  Fe3+ transport in osteoclast differentiation and function.

Representative Publications

Wang L, Fang B, Fujiwara T, Krager K, Gorantla A, Li C, Feng JQ, Jennings ML, Zhou J, Aykin-Burns N, Zhao H. 2018. Deletion of ferroportin in murine myeloid cells increases iron accumulation and stimulates osteoclastogenesis in vitro and in vivo. J Biol Chem 293:9248-9264.

Ficici E, Faraldo-Gómez JD, Jennings ML, Forrest LR. 2017. Asymmetry of inverted-topology repeats in the AE1 anion exchanger suggests an elevator-like mechanism. J Gen Physiol 149: 1149-1164. (Article was featured in editorial comments.)

Myers EJ, Marshall A, Jennings ML, Parker MD. 2016. Mouse Slc4a11 expressed in Xenopus oocytes is an ideally selective H+/OH conductance pathway that is stimulated by rises in intracellular and extracellular pH. Am J Physiol Cell Physiol 311: C945-C959.

Jennings M.L. 2013. Transport of hydrogen sulfide and hydrosulfide anion across the human red blood cell membrane. Rapid H2S diffusion and AE1-mediated Cl/HSexchange. Am J Physiol Cell Physiol 305: C941-C950.

Jennings M.L., Cui J. 2012. Inactivation of Saccharomyces cerevisiae sulfate transporter Sul2p: Use it and lose it. Biophys J 102: 768-776.

Link to Dr. Jennings at PubMed