Four-Legged

cartoon mouse running
Livio Ramondelli

LaToya Carson was only nine years old when she first held a rat by its slender, bald tail. "A woman working at my summer day camp kept a cage of rats and guinea pigs," Carson tells me, a small smile creeping across her lips. "My favorite rat, Vicky, had red eyes and soft white fur."

Little did Carson know that ten years later her relationship with rats would begin anew. Carson, an undergraduate majoring in kinesiology at Penn State, studies how exercise helps the heart protect itself from the damage brought on by disease.

Cardiovascular disease, the number-one killer in the United States for the past 100 years, invades and causes the deterioration of the heart muscle. The term includes atherosclerosis, high blood pressure, congestive heart failure, and more. For decades, Americans have attempted to cut cigarette use, high cholesterol levels, and obesity in hopes of avoiding heart disease. In recent years, the focus has been on exercise. Scientists believe that a history of exercise will make the heart more able to protect itself from disease. In addition, if and when the heart does undergo damage, exercise will provide a back-up system, resulting in a heart that is better prepared to face an attack. But how much exercise is necessary? Carson is working with Penn State physiology and kinesiology professor Donna Korzick to try to find out.

In navy blue wind pants and a white turtleneck, Korzick looks ready for a jog in the brisk winter evening as she stands inside the lobby of Noll Laboratory.

"After this I'm going to Phys-Ed night at my goddaughter's school," she explains enthusiastically. "I wouldn't miss it for the world." Korzick turns and walks quickly down the long, vacant hallway. I follow, always somehow a step behind her.

Reaching her office, she takes a seat behind a desk covered with stacks of photocopied research papers and brightly bound journals and textbooks. A life-sized model of the human heart sits on the corner of the desk.

Raising a scientific journal off her desk, Korzick begins, "In 1996, the Surgeon General reported that if you exercise, you will live longer." Forcefully throwing the journal aside, so that its paper cover smacks hard against the floor of the office, she raises her voice, "That was six years ago. "Exercise makes the heart less prone to heart attacks, less likely to develop heart failure," Korzick says. "Now, we need to figure out why."

Scientists like Korzick believe exercise in some way acts on specific enzymes of the heart. Enzymes are proteins that help to carry out the many chemical processes of the body. Like dominoes tumbling one after another, these molecules move through the cell, making possible a series of reactions. These reactions help keep the body and its cells in good health.

Although many enzymes seem to play an important role in protecting the heart, Korzick and Carson are focusing on multiple forms of an enzyme known as protein kinase C, or PKC. When PKC travels from the cell's cytoplasm (or "insides") to the cell membrane (or "skin"), it becomes activated. Activation jump-starts the enzyme, forcing it to carry out its functional role in the heart. The heart's contractile function—the force of the heartbeat—depends in large part on this activated PKC.

"In old hearts as well as diseased hearts, the contractile function is reduced," Carson explains. Although PKC remains present inside the cells of these weak hearts, it is not activated—no one turns on its switch. Left in the dark, the inactive PKC refuses to move to the cell membrane. The force of the heart's beat decreases. When faced with serious damage, such as a heart attack, a strong heartbeat cannot be maintained.

cartoon mouse lifting weight
Livio Ramondelli

"If the heart beats to full potential it's less prone to heart attacks," Carson explains. Although scientists suspect PKC has many roles following its activation, its role in cardio-protection stems from its influences on the mitochondria. The mitochondria or "powerhouses of the cell," are where ATP, the molecule that provides energy to the cell, is made. Victims of heart attacks tend to have mitochondria with "leaky electrical channels," Korzick says. These leaky channels allow calcium ions to flow into the mitochondria, disrupting the process of ATP production in the cell. With less ATP—less energy—the heart is unable to contract with its usual force. PKC seals the leaks in the electric channels of the mitochondria, keeping the heart strong.

Exercise somehow flips the switch to turn on PKC, causing the movement of the enzyme into the cell membrane, leading to the enzyme's activation. Using rats, Carson hopes to determine the amount of exercise needed to activate PKC, as well as tracing the movement of PKC in cells over time.

It's a blustery afternoon when Carson and I travel to the laboratory. We walk down a set of stairs and through a silent hallway until we reach a locked door. Withdrawing a set of keys, Carson unlocks the room. As the keys jingle, I hear slight movement from within. The sour scent of ammonia mixed with cedar cuts through the air as Carson pushes open the door. Looking up, I see multiple pairs of sleepy red eyes staring intently back at us. Because rats are nocturnal animals, they are probably less than excited to see us this afternoon. Cuddled snuggly together, two to a cage, these furry, white creatures have come to know that when Carson arrives it's time for their daily exercise. Quickly scanning the shelf of cages, Carson notices a rat without a partner.

"This is Rat Number One," she says picking up the cage. With widened red eyes, Rat Number One looks to be the perfect volunteer.

Cage in hand, Carson leads me out of the room and down the hall to a second room, the rat's exercise room. She turns on the light. On two small tables sit individual treadmill belts, each divided into eight lanes by plastic dividers and covers. Lifting one of the plastic lids of the lane, Carson motions, "You just place the rats on the treadmill and turn on the belt." She flicks on the machine's switch. The treadmill groans as it slowly begins to move. Today, however, Rat Number One is in luck—we're just visiting, so he won't have to run his laps.

Turning the treadmill off, Carson turns to Rat Number One's cage. Removing the lid of the cage she reaches in and quickly grasps the rat's tail. She places the rat upon a section of the treadmill and closes its lid. The rat, skeptical, explores the scene, pacing up and down the still treadmill, poking his nose out of the air holes in the plastic dividers.

For three straight months, five days a week, a group of Carson's rats participated in an early morning jog on the treadmill for one hour. This group of rats included young adults, around three months old, and 24-month-old rats, equivalent to 85-year-old humans. Like members at a fitness club after a long holiday break, Carson's rats didn't always seem enthusiastic about their morning workouts. Over time, they learned, Carson saw, gradually becoming good sports.

Carson plans on comparing the rats that ran for one day, one week, or three months to the inactive rats that just sat still on the treadmill. She expects to see an increase in the levels of PKC in the heart-cell membranes proportional with the amount the rats exercised. Carson will be looking at the immediate movement of PKC to the membrane following exercise as well as the movement seen 24 hours following exercise.

Although scientists like Korzick and Carson are slowly unraveling the numerous benefits of maintaining a physically fit heart, Carson is quick to add that her research isn't suggesting that people who fail to exercise are doomed. Exercise is not the save-all plan for living a healthy, carefree life.

"People who don't exercise may not necessarily be at a disadvantage over others," Carson explains. "People who do exercise, on the other hand, are at an advantage. If something goes wrong, their hearts are ready to fight back. It's kind of like people who take vitamin C to decrease the chances of developing a cold," she suggests. Carson believes that exercise can decrease the likelihood of heart problems in the future.

cartoon mouse lifting barbell
Livio Ramondelli

"PKC itself is so huge," Carson says. "We're only tackling a small piece in the understanding of its role in the heart." She describes the process of uncovering the roles of the different forms of the enzyme as "a tag team" effort in the scientific world. Between many laboratories, the scientists hope to one day understand PKC and its role in exercise to its entirety. As Korzick has said, "If we can get people to exercise, we can improve the quality of life."

With plans to attend medical school, Carson admits that she never imagined she would be playing such an important role as an undergraduate scientist. Yet last March, scientists from the American Physiological Society recognized Carson's hard work and awarded her an undergraduate research fellowship to conduct more research on the PKC enzyme over the summer months.

"LaToya's work will make a unique contribution to the science community," Korzick has said. "She makes me want to be a better scientist."

Now as Carson transfers Rat Number One from the treadmill back into his proper cage, she grasps his tail with authority.

"You don't want to grab the tail too close or too far from their bodies," Carson says, suspending the rat in air. Like a bungee jumper soaring through the air, Rat Number One holds his tiny limbs out in search of the earth. She gently puts him in his cage and carries him back to the rat room. As his cage is placed among the other cages, Rat Number One quickly moves to examine his new location. Satisfied, he buries his head underneath the cedar chips covering the floor. Otherwise, all rat eyes are on me as I near the shelf of plastic cages. I marvel at these serene creatures with their smooth white coats and deep clear eyes. Like week-old kittens, the rats nestle close together, unaware of their influential role in helping scientists understand the human heart.

LaToya Carson will receive her B.S. in kinesiology with honors in December 2002 from the College of Health and Human Development and the Schreyer Honors College. Her adviser is Donna H. Korzick, Ph.D., assistant professor of physiology and kinesiology, 106 Noll Lab, University Park, PA 16802; 814-865-5679; dhk102@psu.edu. Funding provided by the National Institutes of Health.

Last Updated January 10, 2014