Role Of Ion Channels In Physiology

Ion channels are membrane proteins that catalyze the transfer of ions down their electrochemical gradients across the plasma membrane. Ion channels are necessary because the plasma membrane is hydrophobic and thus by themselves they are impermeable to ions. In this article, we review what is known about the role of ion channels in physiology and their structure and function. More is known about some ion channels than others. In the last section, we introduce some of the major ion channel families that have attracted the interest of scientists who study ion channels.

There are two types of proteins that are able to move ions across the plasma membrane: ion pumps and ion channels. There are several features that distinguish them. Ion pumps are able to perform thermodynamic work (i.e., they are able to move an ion against its electrochemical gradient). This is accomplished by consuming energy in the form of ATP hydrolysis or the concentration gradients of other ions. Ion channels cannot perform thermodynamic work and the direction of ions traveling through an open channel is solely dependent on the electrochemical gradient. Sometimes ion pumps are said to carry out active transport, whereas ion channels carry out passive transport. Another major difference is the rate at which ions move through these proteins. Ion channels are essentially pores in the plasma membrane and the throughput of an ion channel can be fast—up to 100 million ions per second. The turnover rate of ion pumps is typically orders of magnitude slower.

Ion channels are found in nearly all cells in nature and play integral roles in a cell's basic physiology. It is likely that ion channels were among the proteins found

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in the earliest forms of life on this planet. Through millions of years of evolution, the number and diversity of ion channels have expanded to take on more complex functions such as those involved in learning and memory in the nervous system. Classically, ion channels are introduced via a discussion of neuronal action potentials that transmit signals down an axon. Beyond action potentials, ion channels play roles in other processes too many to enumerate. On a fundamental level, the activity of ion channels can change the membrane potential of the cell or alter the concentrations of ions inside the cell. These processes are basic to the cell's physiology; therefore, it is easily imagined that ion channels may be involved, directly or indirectly, in virtually all cellular activities. More directly, some of these activities may include setting the membrane potential, allowing the entry of ions for nutritive needs, allowing the entry of Ca2 + , which is used as a second messenger, and controlling cell volume.

In other cases, the physiological role of an ion channel is unknown. We have often learned about the function of ion channels by discovering instances when their activity goes awry—namely, disease states. It is becoming apparent that defective ion channels underlie the pathogenesis ofmany human diseases. The term channelopathy has been coined to refer to the expanding list of diseases in this class. For example, cystic fibrosis stems from a mutation in a chloride channel, cystic fibrosis transmembrane regulator (CFTR). In the lung, mutations in CFTR disrupt normal Cl_ efflux, which is necessary for the secretion of fluid that coats the airway epithelium. Consequently, patients with cystic fibrosis develop viscous mucus secretions that can obstruct the airways and are prone to acquiring life-threatening pulmonary infections. Another example is long-QT syndrome. Individuals with long-QT syndrome have abnormally prolonged action potentials in the heart and are at risk for ventricular arrhythmias that can lead to sudden death. Some individuals with long-QT syndrome have mutations in potassium channels that repolarize the cardiac muscle. The direct importance of ion channels in cardiac function is underscored by the effectiveness of antiar-rhythmic drugs, many of which act on ion channels.



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