Ganong's Review of Medical Physiology, 23rd Edition

46 SECTION ICellular & Molecular Basis of Medical Physiology

often external (eg, a neurotransmitter or a hormone). How-
ever, it can also be internal; intracellular Ca2+, cAMP, lipids,
or one of the G proteins produced in cells can bind directly to
channels and activate them. Some channels are also opened
by mechanical stretch, and these mechanosensitive channels
play an important role in cell movement.
Other transport proteins are carriers that bind ions and
other molecules and then change their configuration, moving

the bound molecule from one side of the cell membrane to the

other. Molecules move from areas of high concentration to

areas of low concentration (down their chemical gradient),

and cations move to negatively charged areas whereas anions

move to positively charged areas (down their electrical gradi-

ent). When carrier proteins move substances in the direction of

their chemical or electrical gradients, no energy input is

required and the process is called facilitated diffusion. A typi-

cal example is glucose transport by the glucose transporter,

which moves glucose down its concentration gradient from the

ECF to the cytoplasm of the cell. Other carriers transport sub-

stances against their electrical and chemical gradients. This

form of transport requires energy and is called active trans-

port. In animal cells, the energy is provided almost exclusively

by hydrolysis of ATP. Not surprisingly, therefore, many carrier

molecules are ATPases, enzymes that catalyze the hydrolysis of

ATP. One of these ATPases is sodium–potassium adenosine

triphosphatase (Na, K ATPase), which is also known as the

Na, K pump. There are also H, K ATPases in the gastric

mucosa and the renal tubules. Ca2+ATPase pumps Ca2+ out of

cells. Proton ATPases acidify many intracellular organelles,

including parts of the Golgi complex and lysosomes.

Some of the transport proteins are called uniports because

they transport only one substance. Others are called symports

because transport requires the binding of more than one sub-

stance to the transport protein and the substances are trans-

ported across the membrane together. An example is the

symport in the intestinal mucosa that is responsible for the

cotransport by facilitated diffusion of Na+ and glucose from the

intestinal lumen into mucosal cells. Other transporters are called

antiports because they exchange one substance for another.

ION CHANNELS

There are ion channels specific for K+, Na+, Ca2+, and Cl–, as

well as channels that are nonselective for cations or anions.

Each type of channel exists in multiple forms with diverse

properties. Most are made up of identical or very similar sub-

units. Figure 2–16 shows the multiunit structure of various

channels in diagrammatic cross-section.

Most K+ channels are tetramers, with each of the four sub-

units forming part of the pore through which K+ ions pass.

Structural analysis of a bacterial voltage-gated K+ channel

indicates that each of the four subunits have a paddle-like

extension containing four charges. When the channel is

closed, these extensions are near the negatively charged inte-

rior of the cell. When the membrane potential is reduced, the

paddles containing the charges bend through the membrane

to its exterior surface, causing the channel to open. The bacte-

rial K+ channel is very similar to the voltage-gated K+ chan-

nels in a wide variety of species, including mammals. In the

acetylcholine ion channel and other ligand-gated cation or

anion channels, five subunits make up the pore. Members of

the ClC family of Cl– channels are dimers, but they have two

pores, one in each subunit. Finally, aquaporins are tetramers

FIGURE 2–15 Regulation of gating in ion channels. Several
types of gating are shown for ion channels. A) Ligand-gated channels
open in response to ligand binding. B) Protein phosphorylation or de-
phosphorylation regulate opening and closing of some ion channels.
C) Changes in membrane potential alter channel openings. D) Me-
chanical stretch of the membrane results in channel opening. (Repro-
duced with permission from Kandel ER, Schwartz JH, Jessell TM [editors]: Principles of
Neural Science, 4th ed. McGraw-Hill, 2000.)

Pi P

Closed

A Ligand-gated

Open

B Phosphorylation-gated

C Voltage-gated

D Stretch or pressure-gated

Bind ligand

Stretch

Cytoskeleton

Phosphorylate

Change

membrane

potential

Dephosphorylate

+ ++ +

+ ++ +

• – – –


• – – –