CELL SIGNALING
In addition to their roles in electrical impulse generation and conduction and the maintenance of appropriate fluid balance across cell membranes, ion channels also play a role in certain cell signaling processes. Specifically, the influx of calcium into various cells serves as an activator of these cells. Two examples of such ion channel mediated cellular signaling are described below.
Glucose-dependent Insulin Release in Pancreatic Beta Cells
The pancreas is the central organ responsible for maintaining a normal level of glucose in the bloodstream. Certain cells in the pancreas, called beta cells, secrete insulin in response to an increase in the level of glucose in the bloodstream. Insulin serves to signal other cells in the body to absorb and utilize glucose, whether for increased metabolism, temporary storage as glycogen, or long-term storage as fat.
Certain ion channels in the beta cells of the pancreas play an important role in the secretion of insulin. Following increases in plasma glucose, glucose is taken up into the beta cells via a glucose transporter. Glucose metabolism results in increased production of adenosine triphosphate, or ATP. ATP in turn serves to block the activity of certain potassium ion channels, known as potassium-ATP channels, that are responsible for setting the resting membrane potential of these cells. Because these potassium-ATP channels are blocked, the membrane potential of the cell depolarizes, thereby activating certain voltage-sensitive calcium channels and allowing calcium entry into the cell. The entry of calcium into the cell is the key triggering event that results in the secretion of insulin from the beta cells. The sulfonylureas, a class of drugs used in the treatment of diabetes, exert their activity by directly blocking the potassium-ATP channel, thus resulting in a sustained increase in calcium levels in the cell, thereby leading to increased secretion of insulin.
T-cell Proliferation and Cytokine Production
T-cells play a critical role in the immune response. In addition to their normal protective role, inappropriate or pathologic activation of T-cells also plays an important role in a variety of auto-immune and inflammatory disorders, including rheumatoid arthritis, Crohn's disease, psoriasis and many others.
Certain ion channels located on the surface of particular types of T-cells are believed to play a role in the activation of these cells. Through a series of steps, calcium enters T-cells through various ion channels. This influx of calcium causes the activation of certain factors, which leads to the proliferation of T-cells and the release of certain cytokines.
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