CONTACT: JENNIFER BROWN
Iowa City IA 52242
(319) 335-9917; fax(319) 335-8034
Release: Dec. 7, 2000
UI study suggests different forms of a protein regulate
IOWA CITY, Iowa -- University of Iowa researchers
who study uterine contractions at a molecular level have made a finding that
could provide insight into preventing pre-term contractions.
The researchers, led by Sarah K. England, Ph.D., UI
assistant professor of physiology and biophysics, are investigating a protein
involved in controlling uterine contractions. The so-called maxi-K channel
protein forms pores, or channels, in cell membranes that allow potassium ions
to flow out of cells.
"We know that when these channels are open, the uterus
relaxes and when the channels are closed, the uterus contracts," England said.
"But we don't know precisely how this channel is regulated during pregnancy."
During labor it is critical that the muscles of the
uterus contract. However, it is equally important that those muscles remain
relaxed during the preceding phases of pregnancy. To better understand the
role of the maxi-K channel in controlling uterine excitability and contractility
during pregnancy, the researchers studied the channel protein in mouse uterine
smooth muscle at multiple stages of pregnancy.
"The channels in mice seem to be regulated in a similar
way to those in humans, making the mouse a good model for studying this process,"
England and her colleagues found that the total amount
of channel protein increased during gestation. However, the flow of potassium
ions, a measure of the number of open channels, decreased. This indicated
that the maxi-K channelCHANNEL proteins have somehow been modified such that
the channels do not open so readily.
Previous work, in both humans and mice, has shown
that this protein is normally present in uterine tissue in multiple forms
(isoforms). A biological mechanism known as alternative splicing causes different
forms of the protein to be made. These variants are very similar but they
have different sensitivities to factors such as calcium levels and voltage,
which regulate channel action.
The researchers could not directly measure the amounts
of each protein isoform. Instead, they measured the levels of the genetic
molecule, which encodes for each protein, at different times during pregnancy.
England's team found that different amounts of the various forms are present
at different times during pregnancy. The study also found that one form of
the channel protein, which is less sensitive to calcium and voltage, seems
to be more prevalent at the end of pregnancy. The decreased sensitivity means
that the channels are more often closed than open, causing the uterine muscles
"The increased levels of this isoform toward the end
of gestation would allow the uterus to contract more efficiently and allow
the labor process to ensue," England said.
In addition to their on-going efforts to understand
how modulation of the levels of the
maxi-K protein isoforms alters the excitability and contractility of uterine
tissue, the research team also plans to investigate the role hormones associated
with pregnancy play in this process.
"We hope that drugs could ultimately be designed to
interact specifically with this protein to treat pre-term contractions," England
said. "The goal of our research is to fully understand the regulation of this
channel in uterine tissue so we can better define targets for potential drugs."
The UI study appeared in the September 8 issue of
the Journal of Biological Chemistry. Nancy A. Benkusky, a research assistant
in England's lab, was the lead author. The work was funded by grants from
the National Institutes of Health and the National Science Foundation.
University of Iowa Health Care describes the partnership
between the UI College of Medicine and the UI Hospitals and Clinics and the
patient care, medical education and research programs and services they provide.