Chemistry Reference
In-Depth Information
SODIUM VERSUS POTASSIUM
Sodium and potassium are relatively abundant in the earth's crust, although sodium is much more prevalent in
seawater. The Na
þ
and K
þ
content in the average man represent about 1.4 g/kg and 2.0 g/kg, making them among
the most important of metal ions in terms of concentration. However, their distribution is quite different. Whereas
in most mammalian cells, 98% of K
þ
is intracellular, for Na
þ
the situation is the reverse. This concentration
differential ensures a number of major biological processes, such as cellular osmotic balance, signal transduction,
and neurotransmission. It is maintained by the (Na
þ
-K
þ
)-ATPase, which we will discuss below. However, despite
the presence of only 2% of total body K
þ
outside of cells, this extracellular K
þ
concentration plays a major role in
maintaining the cellular membrane resting potential. Fluxes of these alkali metal ions play a crucial role in the
transmission of nervous impulses both within the brain and from the brain to other parts of the body (Chapter 20).
The opening and closing of gated ion channels (gated channels), which are closed in the resting state, and which
open in response to changes in membrane potential, generate electrochemical gradients across the plasma
membranes of neurons. A nerve impulse is constituted by a wave of transient depolarisation/re-polarisation of
membranes which traverses the nerve cell, and is designated an action potential.
Hodgkin and Huxley (1952)
demonstrated that a microelectrode implanted into an axon (the long process emanating from the body of a nerve
cell) can record an action potential (
Figure 9.1
(a)). In the first
w
0.5 ms, the membrane potential increases from
around
30 mV, followed by a rapid repolarisation, which overshoots the resting potential
(hyperpolarisation) before slowly recovering. The action potential results from a rapid and transient increase in
Na
þ
permeability followed by a more prolonged increase in K
þ
permeability (
Figure 9.1
(
b)). The opening and
closing of these gated Na
þ
and K
þ
ion channels in the axonal membranes create the action potentials (essentially
electrochemical gradients) across these membranes, which allows information transfer and also regulates cellular
function.
The regulation of the flow of ions across cell membranes is absolutely essential for the functioning of living
cells. Because of the hydrophobicity of cellular membranes (as we saw earlier) the energetically driven preference
of ionic species such as Na
þ
K
þ
,Cl
e
,H
þ
, and Ca
2
þ
to cross, never mind to find themselves preferentially on one
side or other of a biological membrane, would be impossible. Without ionic gradients, which maintain high
concentrations of K
þ
within the cell and low concentrations of Na
þ
, cells would not be able to carry out their
normal metabolic activities. This means, in simplistic terms, that some molecular machines must be able to
distinguish between Na
þ
and K
þ
ions (presumably unhydrated, since the degree of hydration could make for
difficulties in discrimination). So, before even beginning a discussion of 'active' transport proteins, whether ion
pumps or ion exchangers, we ask the question how do potential transporters distinguish between these two closely
related cations?
We begin by a reminder that studies over the last 50 years of synthetic and naturally occurring ion-binding
small molecules (host/guest chemistry with ions) have established the basic rules of ion selectivity within small
molecules. Two major factors are important in ion selectivity
e
60 mV to about
þ
the atomic composition and the stereochemistry
(e.g., the size) of the binding site. Using synthetic chemistry, molecules have been created of a given class with
selectivity favouring Li
þ
(radius 0.60
˚
), Na
þ
(radius 0.95
˚
), K
þ
(radius 1.33
˚
), and Rb
þ
(radius 1.48
˚
)by
simply adjusting the cavity size to match the ion (
Dietrich, 1985
).
1
Now that we have high-resolution crystal structures of membrane transport proteins, we can begin to
understand how ion selectivity is accomplished. In
Figure 9.2
the Na
þ
-selective binding sites in the Na
þ
-
dependent leucine transporter LeuT and the K
þ
-selective binding sites in the K
þ
channel provide a direct
comparison of selectivity for Na
þ
- and K
þ
.
LeuT transports leucine and Na
þ
across the cell membrane using the energy of the Na
þ
gradient to pump
leucine into the cell. The structure (
Figure 9.2
(
a)) shows a leucine and two Na
þ
ions bound deep inside the protein,
e
1. The author remarked that this was particularly easy for the alkali metals of group 1A because the differences in ionic radius are greatest
(0.35
˚
).
