During this period, Dale published the first of numerous studies on the effect of the diuretic amiloride on sodium transport after being prompted to do the experiments by Sid Simon, who had attended a seminar on the drug. Inhibition of transport by this compound has since become one of the hallmarks used to characterize voltage-insensitive sodium channels.
Donations can be made to the Dale J. Benos Research Fund, c/o UAB Gift Records, 1530 Third Ave. S.,
AB1230, Birmingham, AL, 35294.
In 1978, Dale joined Harvard Medical School as an Andrew W. Mellon scholar in reproductive biology, and his work focused on the mammalian blastocyst; although his research into sodium transport in frog skin and erythrocytes continued, the latter was something of a personal achievement for someone who hated the sight of blood!
The preimplantation rabbit blastocyst undergoes dramatic changes in Na+ permeability and volume during development, and elucidating the mechanisms involved in this process occupied Dale and colleague Bob Balaban for most of the early 1980s. Dale then began to focus on the Na+ channel itself.
With Sarah Sariban, Latorre, Mo Burg and Lori Olans, Dale isolated the amiloride-sensitive Na+ channel from an amphibian renal cell line A6. Incorporation of the purified protein into a lipid bilayer and the demonstration that this protein formed an amiloride-sensitive Na+ channel resulted in the 1984 publication of a seminal paper in Nature. Subsequent papers in the Proceedings of the National Academy of Sciences, Biochemistry and the Journal of Biological Chemistry, as well as a landmark review co-authored with Haim Garty, described the isolation and characterization of a mammalian Na+ channel complex.
At Harvard, Dale recruited his first graduate student, Juan Reyes, to work on metabolism and transport in spermatozoa. Their finding that gossypol, a component of cottonseed oil, could block oxidative phosphorylation in spermatozoa, and the potential role of gossypol as a male contraceptive, led to an article by Good Housekeeping magazine, an achievement of which Dale was quite proud!
In 1985, he joined the University of Alabama at Birmingham as an associate professor and remained there the rest of his career. He was appointed full professor in 1987 and chairman of the department of physiology and biophysics in 1996.
He continued work on the mammalian Na+ channel and later on ENaC, using bilayers, patch clamp and biochemical approaches. This expanded to include studies of epithelial chloride and sodium transport in the airways, of the effects of the HIV envelope protein gp120 on function of the Na+/H+ exchanger and of the role that glutamate efflux from astrocytes might have on neuronal death and cognitive deficits in AIDS patients. His recent research focused on the role of Na+ transport in glioma cells and was spurred, in part, by illness in his family and the death from a stage IV brain tumor of his friend and mentor Mandel.