5: Ion Channels

Introduction

• Rapid Signaling in the Nervous System Depends on Ion Channels?

• Ion Channels Are Proteins That Span the Cell Membrane

• Currents Through Single Ion Channels Can Be Recorded

• Ion Channels in All Cells Share Several Characteristics

  • The Flux of Ions Through a Channel Is Passive

  • The Opening and Closing of a Channel Involve Conformational Changes

• The Structure of Ion Channels Is Inferred from Biophysical, Biochemical, and Molecular Biological Studies

  • Ion Channels Can Be Grouped into Gene Families

  • The Closed and Open Structures of Potassium Channels Have Been Resolved by X-Ray Crystallography

  • The Structural Basis of Chloride Selectivity Reveals a Close Relation Between Ion Channels and Ion Transporters

• An Overall View

Signaling in the brain depends on the ability of nerve cells to respond to very small stimuli with rapid and large changes in the electrical potential difference across the cell membrane. In sensory cells, the membrane potential changes in response to minute physical stimuli: Receptors in the eye respond to a single photon of light; olfactory neurons detect a single molecule of odorant; and hair cells in the inner ear respond to tiny movements of atomic dimensions. These sensory responses ultimately lead to the firing of an action potential during which the membrane potential changes up to 500 volts per second.

The rapid changes in membrane potential that underlie signaling throughout the nervous system are mediated by ion channels, a class of integral membrane proteins found in all cells of the body. The ion channels of nerve cells are optimally tuned to respond to specific physical and chemical signals. They are also heterogeneous—in different parts of the nervous system different types of channels carry out specific signaling tasks.

Because of their key roles in electrical signaling, malfunctioning of ion channels can cause a wide variety of neurological diseases (see Chapter 14). Diseases caused by ion channel malfunction are not limited to the brain; cystic fibrosis, skeletal muscle disease, and certain types of cardiac arrhythmia, for example, are also caused by ion channel malfunction. Moreover, ion channels are often the site of action of drugs, poisons, or toxins. Thus ion channels have crucial roles in both the normal physiology and pathophysiology of the nervous system.

In addition to ion channels, nerve cells contain a second important class of proteins specialized for moving ions across cell membranes, the ion transporters or pumps. These proteins do not participate in rapid neuronal signaling but rather are important for establishing and maintaining the concentration gradients of physiologically important ions between the inside and outside of the cell. As we will see in this chapter and Chapter 6, ion transporters differ in important aspects from ion channels, but also share certain common features.

Rapid Signaling in the Nervous System Depends on Ion Channels

Ion channels have three important properties: (1) They recognize and select specific ions, (2) ...