Study: calcium channels regulate cell movement

July 21, 1999

CHAPEL HILL - University of North Carolina at Chapel Hill scientists and colleagues, who discovered several years ago that certain cells glide forward in a microscopic version of "moonwalking," have now discovered that calcium channels -- which function when cells stretch -- help regulate cell movement.

The finding one day may have profound clinical implications in wound healing and cancer treatment, the researchers say.

"A lot of people don't realize that many cells are not stationary but can travel from one place to another," said Dr. Juliet Lee, former research assistant professor of cell biology and anatomy at UNC-CH and now assistant professor of molecular and cell biology at the University of Connecticut. "If cells could not move, none of us would exist. Embryos would not develop, wounds would never heal and many tumors could not send off cells to colonize other parts of the body.

"What we've discovered is an important aspect of how that movement occurs," Lee said. "When cells are stretched, such as when they're going forward and their back end gets stuck, calcium channels along the sides open to admit more calcium ions. This boosts the cell's motility so that the back end is pulled away from whatever it's been stuck on, and it can move forward again."

A report on the findings appears in the July 22 issue of the journal Nature. UNC-CH authors are Drs. Gerry Oxford, professor of cell and molecular physiology, and Ken Jacobson, professor of cell biology and anatomy. Dr. Barry Johnson, assistant professor of physiology and neurobiology at UConn, also participated in the studies.

The researchers conducted a complicated series of experiments involving stretching fish skin cells called keratocytes on silicone rubber sheets and measuring the entry of calcium ions into the cells in response to the stretching. During stretching, calcium concentrations inside the cells jumped for periods of three to five seconds, Lee said. Some calcium came from outside the cell, while the rest was released from internal storage sites.

"We also found that if we prevented cells from exhibiting these pulses of calcium, the cells became stuck so they could no longer pull their back edges in, which is necessary for forward movement," she said. "As soon as the rear of the cell retracts, the stretching is released, the calcium channels close and the level of calcium drops back."

Over brief periods, the channels become less responsive to stretching, an adaptation that prevents them from being flooded with calcium that is present in concentrations 1,000 times higher outside cells.

The scientists studied fish skin cells, which Lee called the "Lamborghinis of the cell world," because they move so fast compared to most other cells and must do so to close wounds such as bites fish frequently suffer.

Many other cell types contain stretch-activated calcium channels, and she and her colleagues believe they likely regulate movement of those cells similarly as well.

"For this reason the finding could be of fundamental clinical importance because manipulating those channels in various ways might one day promote wound healing or prevent cancer cells from spreading," Jacobson said.

Unlike normal cells, malignant cancer cells that travel to other parts of the body have lost some of their ability to curb inappropriate movement.

In 1993, Lee, Jacobson -- a member of the UNC Lineberger Comprehensive Cancer Center -- and others published another paper in Nature describing how they employed video microscopy, a technology that marries microscopes to television cameras, to study movement of the keratocyte cells.

The technology revealed that the molecular machinery inside those cells exerted perfectly coordinated and graded extension pressures along the front half of the cell membrane while simultaneously tucking in the back edge. The fastest of the forward extensions acted in the center of the cell's leading edge, opposite to where the fastest tucking occurred in the center of the back edge.

The movement was dubbed "moonwalking" after singer Michael Jackson's distinctive backward gliding motion on stage.
-end-
Note:
Lee's number at UConn is 860-486-4332. She is in Hungary from July 18-23 and will be in London at 44-181-360-6233 until Aug. 3.
Her e-mail address is jlee@uconnvm.uconn.edu.
Jacobson's numbers at UNC-CH are 919-966-5703 and 966-3855.
His e-mail address is frap@med.unc.edu.

Contact:
David Williamson, 919-962-8596.

University of North Carolina at Chapel Hill

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