What are the concentrations
different ions in cells?
of
Beginning biology students are introduced to the macromolecules of the
cell (proteins, nucleic acids, lipids and carbohydrates) as being the key
players in cellular function. What is disturbingly deceptive about this
picture is that it makes no reference to the many ion species without
which cells could not function at all. Ions have a huge variety of roles in
cells. Several of our favorites include the role of ions in electrical
communication (Na+, K+, Ca2+), as cofactors in dictating protein function
with entire classes of metalloproteins (constituting by some estimates at
least ¼ of all proteins) important in processes ranging from
photosynthesis to human respiration (Mn2+, Mg2+, Fe2+), as a stimulus for
signaling and muscle action (Ca2+), and as the basis for setting up
transmembrane potentials that are then used to power key processes
such as ATP synthesis (H+).
The differences in concentration of ions between the cellular interior and
the external milieu are carefully controlled by both channels and pumps.
Ion channels serve as passive barriers that can be opened or closed in
response to environmental cues (such as voltage across the membrane,
the concentration of ligands or membrane tension) and pumps, by way
of contrast, use energy in the form of protons or ATP in order to pump
charged species against their concentration gradient. The differences in
concentration mediated by these membrane machines can often be
several orders of magnitude and in the extreme case of calcium ions
correspond to a 10,000-fold greater concentration of ions outside of the
cell than inside as shown in Table 1. The dominant players in terms of
abundance are potassium (K+), sodium (Na+), chloride (Cl-) and
magnesium (Mg+2) (though the latter is mostly bound to ribosomes and
other macromolecules and its free concentration is much lower). Table 1
shows some typical ionic concentrations in both bacteria and
mammalian cells. One of the provocative observations that emerges
from this table is that positive ions are much more abundant than
negative ions. What is the origin of such an electric imbalance in the
simple ions? Many of the metabolites and macromolecules of the cell are
negatively charged, conferred by phosphate in small metabolites and
DNA and carboxylic groups (in the acidic amino acids). The positive ions
balance the negative charge so that the cell is electroneutral.
Potassium is usually close to equilibrium in animal and plant cells
(Nobel, 2005). Given that its concentration inside the cell is about 10 to
100 fold higher than outside the cell, from equilibrium we can infer that
the cell is negative inside. This is indeed the direction of the voltage
across the cell membrane.
The concentrations described above are in no way static. They vary with
the organism and the environmental and physiological conditions. To
flesh out the significance of these numbers, we explore several case
studies. For example, how different is the charge density in a neuron
before and during the passage of an action potential? As noted above,
the opening of ion channels is tantamount to a transient change in the
permeability of the membrane to charged species. In the presence of
this transiently altered permeability, ions rush across the membrane as
described in detail in the vignette on “How many ions pass through an
ion channel per second?”. But how big a dent does this rush of charge
actually make to the overall concentrations? In fact, a simple estimate
reveals that the change in the internal charge within a cell as a result of
membrane depolarization is only 10-5 Qint , where Qint is the charge within
the cell prior to membrane depolarization, and hence gating of the
relevant channels. This estimate shows how minor absolute changes can
still have major functional implications.
Another way in which the pool of ions and metabolites are critical to the
lives of cells is through their influence on the osmotic pressure. The
membrane of the cell is often thought of as a semi-permeable interface
that enables the steady passage of water molecules while preventing the
transport of ions and metabolites. On closer inspection it turns out that
even water movement is actually often regulated, through pores called
aquaporins and by way of contrast, that some metabolites such as
uncharged glucose have nonvanishing permeability. Nevertheless, we
will allow ourselves to simplify the semi-permeable properties and
further use results on ideal solutions for discussing the osmotic pressure.
The osmotic pressure is the extra pressure that is sustained on the side
of a semi permeable barrier that has a higher concentration of solutes. It
obeys a relation similar to the ideal gas law where the osmotic pressure
p is given by the simple relation (the van’t Hoff relation) p=(N/V) RT,
where N/V is the solute concentration, R is the universal gas constant
and T is the temperature. Instead of plugging numbers into this simple
expression, let us turn instead to simple estimates using some key
numbers and orders of magnitude as shown in Figure 1. First, we use the
fact that the concentration of water is ≈50M. This is ≈1000 times higher
than the concentration of air. For the concentration of air, the pressure
equals one atmosphere. R and T being constants, we can conclude that at
a concentration 1/1000 that of water, i.e. 50mM, we will get an osmotic
pressure of one atmosphere. If we add up the concentration of free ions
(Table 1) and metabolites inside a cell (See table in vignette on
metaoblites concentrations) we find a concentration of roughly 300500mM, implying in turn an osmotic pressure of about 6-10
atmospheres. As a result, putting cells from multicellular organisms in
pure water will often cause them to burst as they cannot adapt to being
out of their buffered intercellular environment. Such cells are grown in
the lab in media that have a total solute concentration that is similar to
that of the cell interior thus ensuring an intact water balance. Bacteria
and plants are usually able to withstand the pressure difference due to
their pressure resisting cell walls. In plants, the osmotic pressure also
known as turgor pressure plays a key part in shaping the posture and
enabling movement of these mostly sessile organisms – the turgor
pressure dictates if our home plant is wilting or astute and enables the
Venus flytrap to snap within 100 ms (BNID 106630) to capture insects to
supplement its diet.
Figure 1: Rule of thumb for the correspondence between osmotic
pressure and solute concentration.
Table 1: Ionic concentrations inside a bacterial cell and inside and outside a
mammalian cell. Concentrations in mM. Numbers in brackets are BNID. Note that
concentrations can change by more than an order of magnitude depending on cell
type and physiological conditions.
Ion
Sea
water
[mM]
(106594)
E. coli [mM]
(107033,
107114)
K+
Na+
≈10
≈500
Mg2+
≈50
30-200
≈200 (free) +
≈200 (bound)
100 (bound)
Ca2+
≈10
10-4
Cl-
≈560
100-200
Mammalian
muscle
cell
[mM]
(103966,
107187)
142
7-15
Concentration
ratio
extracellular to
intracellular
(104083)
1/20-1/40
≈10
10 (bound)
0.6 (free)
10-5
≈10,000
5-30
BNID
104049
104050
104983,
100770,
101953
100130