Insight: Research Edition

Fall 2005

Researchers Hope Tracking Ion Channels Will Give Clues to Cells’ Function

As a biologist, Dr. Michael Tamkun had a keen interest in venomous animals – more precisely, how venom from poisonous animals worked to kill prey. Many venoms, including the venoms of cobras, poison dart frogs, scorpions and sea snakes, act by interfering with ion channel activity, effectively shutting down cell function.

So it was from an early fascination with venomous animals that Dr. Tamkun grew interested in ion channel proteins. Now a Professor in the Department of Biomedical Sciences and a faculty participant with the Program in Molecular, Cellular and Integrative Neurosciences, Dr. Tamkun is studying ion channel proteins to develop a greater understanding of the role these ubiquitous proteins play in different tissue types.

“What my lab is interested in is how ion channel proteins move around in cells,” said Dr. Tamkun. “These are the proteins that are the basis of electrical activity in the nervous system. For example, when a dentist uses lidocaine to numb a tooth, the lidocaine binds with ion channel proteins so they can’t function enabling a dentist to do his work without the patient feeling any sensation of pain.”

For dental patients, that’s a good thing. But ion channel malfunctions are also at the root of a number of devastating diseases including cystic fibrosis and cardiac arrhythmias. Understanding the normal function of ion channel proteins, including how they get to where they are going and how the cell knows where to place them, will lead to a greater understanding of cell biology and perhaps help develop more effective treatments and cures for illnesses that have as a hallmark ion channel irregularities.

“We work mainly with a potassium channel known as Kv2.1, one of 50 members of this family type in the body,” said Dr. Tamkun. “Why we have 50 different genes encoding this type of channel is another question, but it probably is because it gives the cells the capability to regulate electrical excitability in many different ways. What we are doing in our lab is studying how these channels move in living cells using a technique that tethers florescent proteins to the channel. Using a high-resolution fluorescence, confocal microscope, we can then localize and track the ion channel as it moves to and from the cell surface of living neurons and cardiac myocytes.”

What the work of Dr. Tamkun and others has shown is that distinct ion channel proteins are expressed differently in different types of cells, and are always changing. In cardiac cells, for example, the number and location of channel proteins can change from one beat to the next. Researchers also are seeing that discreet domains exist that compartmentalize ion channels. This leads to additional questions about why domains exist, how channels get to specific domains, and how the cells keep channels within those domains.

“We know very little about this dynamic behavior,” said Dr. Tamkun. “The technology simply hasn’t been there to help us answer these questions, but new research methodologies and technological advances are moving us forward so that we may one day delve even deeper into these mysteries of the cell.”

The cells being studied in Dr. Tamkun’s laboratory present research challenges because they are always changing. The brain is always thinking and the heart is always beating so these systems are not static and are always changing the number of proteins from one beat to the next and from one action to the next. New tagging and recording technology is helping researchers see and follow proteins of interest, one day leading to breakthroughs in understanding of the most basic but complex functions of the cell.