CREDIT: COPYRIGHT UC REGENTS/UC DAVIS HEALTH

A protein known to expand blood vessels — key to controlling
conditions like high blood pressure — actually has different
functions in males and females, new UC Davis Health research shows.

Conducted using arterial cells from mice, the study is the first to
identify sex-based distinctions in how the protein –Kv2.1 — works.

Kv2.1 is generally known to form calcium channels that dilate blood
vessels. In arterial cells from female mice, however, it contracted
blood vessels.

The research was led by Luis Fernando Santana, professor and chair of
physiology and membrane biology, and graduate student Samantha
O’Dwyer. It is published in the Proceedings of the National Academy of
Sciences.

“We were shocked at the difference and the strength of that
difference,” Santana said. “We think we’ve found the physiological
explanation for what some of our clinical colleagues are seeing in
patients ? some high blood pressure medications tend to work better
for men, while others work better for women.”

Santana and his team study calcium channels, their effects on heart
muscle cells and how to alter that process to improve treatments for
cardiovascular disease. They are especially interested in finding new
treatments for hypertension, because it affects 45% of adults in the
U.S. and is linked with serious conditions such as stroke, heart
failure and aneurysm.

The current study focused on how Kv2.1 changes calcium channel
organization and function. The investigators found that Kv2.1 promotes
tight clustering of calcium channels. Kv2.1 expression is higher in
cells from female mice, leading to larger clusters. This caused higher
calcium levels in arterial cells and vasoconstriction. In arterial
cells from male mice, Kv2.1 expression was not as high and calcium
channel clusters were much smaller, causing vasodilation.

“This difference can only be attributed to the sex of the research
mice,” Santana said.

The next step, Santana said, is to determine what causes the different
roles of Kv2.1. He plans to investigate the potential that sex
hormones regulate the protein in arterial cells. His ultimate goal is
tailored treatment strategies for hypertension for men and women.

“Until recently, the research community only used male mice to
investigate heart disease,” Santana said. “Our study proves what a
major oversight that has been.”

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Other researchers on the study were Stephanie Palacio, Collin
Matsumoto, Laura Guarina, Nicholas Klug, Sendoa Tajada, Barbara
Rosati, David McKinnon and James Trimmer, all of UC Davis. Rosati also
is affiliated with the State University of New York.

The study was supported by grants from the National Institutes of
Health (grant numbers 5R01HL085686, 1R01HL144071, 1OT2OD026580 and
T32HL086350) and the American Heart Association.

“Kv2.1 Channels Play Opposing Roles in Regulating Membrane Potential,
Ca2+ Channel Function, and Myogenic Tone in Arterial Smooth Muscle” is
available online.

More information about UC Davis Health, including its Department of
Physiology and Membrane Biology,” is available at health.ucdavis.edu.