these concentration gradients requires the
expenditure of energy (adenosine triphos-
phate [ATP] hydrolysis) coupled with ionic
pumps. Consider the concentration gradi-
ents for Na+ and K+. Na+ constantly leaks into
the resting cell, and K+ leaks out. Moreover,
whenever an action potential is generated,
additional Na+ enters the cell and additional
K+ leaves. Although the number of ions mov-
ing across the sarcolemmal membrane in a
single action potential is small relative to the
total number of ions, many action potentials
can lead to a significant change in the extra-
cellular and intracellular concentration of
these ions. To prevent this change from hap-
pening (i.e., to maintain the concentration
gradients for Na+ and K+), an energy (ATP)-
dependent pump system (Na+/K+-adenosine
[ATPase]), located on the
sarcolemma, pumps Na+ out and K+ into the
cell (Fig. 2.2). Normal operation of this pump
is essential to maintain Na+ and K+ concen-
trations across the membrane. If this pump
stops working (such as when ATP is lost
under hypoxic conditions), or if the activity
of the pump is inhibited by cardiac glycosides
such as digoxin, Na+ accumulates within the
cell and intracellular K+ falls. This change
results in a less negative (more depolarized)
resting membrane potential primarily because
becomes less negative (see Equation 2-1).
Besides maintaining the Na+ and K+ concentra-
tion gradients, it is important to note that the
Na+/K+-ATPase pump is electrogenic because
it extrudes three Na+ for every two K+ entering
the cell. By pumping more positive charges
out of the cell than into it, the pump cre-
ates a negative potential within the cell. This
electrogenic potential may be up to -1 0 mV,
depending on the activity of the pump. Inhi-
bition of this pump, therefore, causes depolar-
ization resulting from changes in Na+ and K+
concentration gradients and from the loss of
an electrogenic component of the membrane
potential. In addition, increases in intracellu-
lar Na+ or extracellular K+ stimulate the activ-
ity of the electrogenic Na+/K+-ATPase pump
and produce hyperpolarizing currents.
Because Ca++ enters the cell, especially dur-
ing action potentials, it is necessary to have a
mechanism to maintain its concentration gra-
dient. Two primary mechanisms remove cal-
cium from cells (Fig. 2.2). The first involves
an ATP-dependent Ca++ pump that actively
pumps calcium out of the cell and gener-
ates a small negative electrogenic potential.
= ATP-dependent Ca++
2 = Na+
exchanger (3:1)
3 = Na7K+-ATPase pump (3:2)
■ FIGURE 2.2 Sarcolemmal ion pumps and exchangers. These pumps maintain transmembrane ionic
gradients for Na+, K+, and Ca++. Na+ and Ca++ enter the cell down their electrochemical gradient, especially
during action potentials, while K+ is leaving the cell. Ca++ is removed by an ATP-dependent, electrogenic
Ca++ pump (?) and by the electrogenic Na+/Ca++ exchanger that exchanges three Na+ for every one Ca++ (2).
Na+ is actively removed from the cell by the electrogenic Na+/K+-ATPase pump, which brings two K+ into
the cell for every three Na+ that are pumped out.
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