charge has to be balanced with positive
charges in order to maintain electro-
neutrality, and potassium ions are used for
this. The plasma membrane is relatively
permeable to potassium ions but sodium
ions are actively extruded by the sodium
pump. Thus a gradient is maintained, with
extracellular and intracellular concentra-
tions of Na+being 120 and 10 mM, respec-
tively, and of K+being 2.5 and 140 mM,
respectively. This gradient or disequilib-
rium of sodium ions provides the driving
force that cells are able to use to control
and alter their intracellular environment.
Maintenance of this Na+gradient in the
face of both active and passive influx of
Na+into the cell is energetically expensive.
Additionally, the concentration gradient of
K+, together with the relative permeability
of the plasma membrane to K+, generates
the resting electrochemical gradient across
the plasma membrane of cells as K+dif-
fuses out more quickly than other posi-
tively charged ions can diffuse in (Eckert
and Randall, 1983).
Sodium/Proton Exchange
All cell membranes contain embedded
proteins that exchange sodium ions for
protons across the plasma membrane in a
fixed ratio of one Na+for one H+. It is
accepted that the main mechanism for
proton extrusion is the Na+/H+antiporter
which uses energy stored in the Na+
gradient to pump protons out from the
intracellular space (Graf et al., 1988). The
activity of this antiporter is determined by
the intracellular pH (pHi) and it serves to
protect cells against acidification of the
cytosol (Pouyssegur et al., 1988). At pHi
>7.4, this antiporter is virtually inactive
but, as the pHi decreases from 7.4, the
activity of the antiporter increases, reach-
ing a maximum at a pHiof 6.0.HormonesMany of the hormones which stimulate
anabolic processes in cells (mitogens or
growth factors) have been shown to cause
an increase in pHi. This change is typically
0.15–0.3 pH units, representing a consider-
able decrease in the intracellular proton
concentration. Such a change will, by itself,
influence the activity of many metabolic
pathways due to the pH sensitivity of many
key enzymes. Pouyssegur et al. (1988)
proposed a mechanism whereby binding of
these hormones to receptors on the cell
surface caused activation of protein kinase
C (in the case of thrombin, bombesin,152 N.S. Jessop
Fig. 7.1.Schematic diagram illustrating how various factors represented along the bottom row can influence
the rate at which Na+enters a cell across the plasma membrane. To maintain steady-state concentrations of
Na+within the cell, the rate at which Na+is pumped from the cell by Na+,K+-ATPase must equal the rate of
entry of Na+. The energetic cost of such pumping is one-third of a molecule of ATP per Na+expelled.