5 ion channels

abstract

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 selectively reveals a close relation between ion channels and ion transporters

an overall view

content

100

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

rapid signaling in the nervous system depends on ion channels

101

many channels open and close in response to a specific event: voltage-gated channels are regulated by changes in membrane potential, ligand-gated channels by chemical tansmitters, and mechanically gated channels by pressure or stretch. however, some channels are normally open in the cell at rest. the ion flux through these “resting” channels contributes significantly to the resting potential

101

different types of ion pumps maintain the concentration gradients for Na+, K+, Ca2+, CL-, and other ions

101

these pumps differ from ion channels in two important details. first, whereas open ion channels have a continuous water-filled pathway through which ions flow unimpeded from one side of the membrane to the other, each time a pump moves an ion, or a group of a few ions, across the membrane, it must undergo a series of conformational changes. as a result, the rate of ion flow through pumps is 100 to 100,000 times slower than through channels. second, pumps that maintain ion gradients use energy, often in the form of adenosine triphosphate (ATP), to transport ions against their electrical and chemical gradients. such ion movements are termed active transport. the function and structure of ion pumps is considered in detail at the end of this chapter and in chapter 6

ion channels are proteins that span the cell membrane

currents through single ion channels can be recorded

all 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

113

the great diversity of ion channels in a multicellular organism is underscored by the recent sequencing of the human genome. our genome contains nine genes encoding variants of voltage-gated Na+ channels, 10 genes for different Ca2+ channels, over 75 genes for K+ channels, 70 genes for ligand-gated channels, and more than a dozen genes for Cl- channels. fortunately, the evolutionary relationship between the genes that encode ion channels provide a relatively simple framework with which to categorize them
most of the ion channels that have been described in nerve and muscle cells fall into a few gene superfamilies. members of each gene superfamily have similar amino acid sequences and transmembrane topology and, importantly, related functions. each superfamily is thought to have evolved from a common ancestral gene by gene duplication and divergence. several superfamilies can be further classified into families of genes with more closely related structure and function

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

the vertebrate CIC family of chloride channels and transporters are double-barrel channels with two identical pores

an overall view

124

the activity of channels can be modified by cellular metabolic reactions, including protein phosphorylation; by various ions that act as blockers; and by toxins, poisons, and drugs. channels are also important targets in various diseases