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Overview. Cell:cell communication is essential for multicellular life and can take many forms. For example, during development, our body's cells may communicate using chemicals called hormones so that sex-specific structures are built. At other times our cells may need to communicate quickly over long distances (say from our foot to our head and back again). In these cases, our body will require the use of excitable cells that send electrical signals. Essentially my research concerns how a cell can generate such electrical signals.

What is an excitable cell? All cells maintain an electrical difference across their cell membrane. This is done in order to optimize the conditions in the cell for various cellular processes. The electrical difference across the membrane arises because various ions, such as potassium, sodium, and calcium, are present in different concentrations on the two sides of the membrane. Since these ions are charged, this concentration difference ultimately results in an electrical difference across the cell membrane (called a membrane potential). A typical cell is said to be polarized in that it is more negative on the inside relative to the outside. Normally this electrical difference, or membrane potential, will not change very much or very quickly. However, excitable cells can rapidly change their membrane potential in response to a signal. It is this ability to change their membrane potential that gives the most familiar excitable cells, neurons, the ability to store, recall, and distribute information.

How do these rapid electrical changes across the membrane occur? When excitable cells rapidly change their membrane potential they are said to be undergoing an action potential. Simply put, this refers to the dynamic (action) changes that are occurring to their membrane potential over time. These changes occur rapidly (from milliseconds to seconds in duration). A typical action potential starts when positive ions come into a cell, depolarizing it (making it less negative). At some point, the cell reverses the depolarization and begins to repolarize the cell (bringing it back to a more negative or polarized state). Underlying the control of these membrane potential changes are proteins that are imbedded in the cell membrane that function as a set of pores or channels that can be opened and closed by the cell. The opening and closing of these channels allow ions to move across the membrane and thus allow electrical currents to flow across the membrane. These currents act to depolarize and then repolarize the cell.

The ion channels operate in a tightly choreographed sequence that is controlled by additional proteins that must interact with these ion channels (to either open or close them). It is important that these channels open and close in the proper way in order for a cell to respond correctly to a given stimulus. For example, if the channels that act to repolarize the cell open too soon, that cell's response may be inappropriately shortened. Identifying the additional proteins which are involved in regulating the opening and closing of these channels is the subject of much research in biology (including my own). The ultimate goal of this work is to obtain a detailed molecular picture of this process which may perhaps provide insight into disorders of the nervous system.

 

Understanding this process at the molecular level. In complicated systems, such as human nerve cells, cellular and molecular researchers attempt to understand this process using a 'grind and find' sort of approach. Essentially, researchers isolate various proteins and then test for activity that is relevant to nerve cell function. While this method has certain advantages, it is also a slow process, one which is technically difficult and prone to artifacts. An alternative approach is to find a simpler system with similar features that is amenable to a genetic approach.

Genetically amenable systems allow one to isolate mutants that have been altered in their ability to do some process. By understanding what has gone wrong in such mutants, we gain a better understanding of what is important for that process to proceed properly. One system in which it is possible to undertake a genetic approach to understanding how a cell initiates and regulates an action potential is the ciliated protozoan, Paramecium tetraurelia (Paramecium).

Paramecium is a single celled organism that has a collection of simple behaviors which allow it to move through its environment, find food, and avoid predators. Underlying the control of these simple behaviors is an action potential that is similar to that found in the excitable cells of higher organisms (Hinrichsen and Schultz, 1988). When an action potential is initiated, the cell will swim backwards for a length of time that is directly proportional to the duration of the action potential (i.e., the length of time that the cell is depolarized).


Last updated Wednesday July 18, 2001 Webmaster Dean Fraga.