Biomedical Engineering Reference
In-Depth Information
pharmacological modulation and constitute important targets for drug treatment of diverse diseases
including cardiac arrhythmia, arterial hypertension, diabetes, seizures, and anxiety.
13.1.1 I
ON
C
HANNELS
A
RE
P
ORES
THROUGH
THE
C
ELL
M
EMBRANE
The cell membrane is impermeable to the small ions since they are charged. The ions polarize
the water molecules around them and carry a shell of hydration water rendering them insoluble
in the hydrophobic phospholipid membrane. Ion transport in and out of cells has to occur through
specialized molecules, allowing the cells to compose a specii c intracellular ion-milieu, which
in many ways is different from the extracellular ion-milieu, e.g., there is more than a 10-fold
gradient in the Na
+
- and K
+
-concentrations and a 10,000-fold gradient for Ca
2+
across the cell
membrane (Table 13.1).
The membrane proteins establishing these gradients are transporters such as the Na-K ATPase
pumping three Na
+
out and two K
+
into the cell while consuming one ATP molecule. Other trans-
porters are the Ca-ATPases pumping Ca
2+
out of the cell or into the endoplasmic reticulum, and
secondary active transporters such as the Na-Ca exchanger not using energy themselves but exploit-
ing the gradients created by the ATPases. The transporters typically move 0.1-10 ions/ms each, they
show saturation kinetics like enzymes, and they slowly build up the ion gradients.
The ion channels are different in many ways. They form water-i lled pores through the cell
membrane once they open, and permeation through the channels is only limited by diffusion. The
transport is very fast, in the range of 10
4
-10
5
ions/ms, and the opening of ion channels may change
the membrane potential by 100 mV within less than 1 ms. Ion channels are thus in an ideal position
to govern the fast electrical activity of cells.
TABLE 13.1
Typical Intra- and Extracellular Ion Concentrations
and Corresponding Equilibrium Potentials
Intracellular
Concentration (mM)
Extracellular
Concentration (mM)
Equilibrium
Potential (mV)
Ion
Ca
2+
0.0001
1-2
+120
Na
+
10
145
+70
Cl
−
10
110
−62
K
+
140
4
−93
13.1.2 I
ON
C
URRENTS
C
HANGE
THE
E
LECTRICAL
M
EMBRANE
P
OTENTIAL
In biological tissue electrical currents are conducted by the movement of ions. Bulk movements of
ions in organs give rise to large currents resulting in voltage differences that can be measured
on the body surface as was i rst done by Willem Einthoven in 1901 when he recorded human
electrocardiograms. At the cellular level, the nature of excitable ion currents through the cell membrane
was demonstrated by Hodgkin and Huxley in 1953 using a preparation of the squid axon. This giant
nerve axon is about 1 mm in diameter, i.e., about 1000-fold thicker than human axons allowing
electrodes to be positioned on either side of the membrane and the ion compositions on both sides
to be controlled. Using this method the authors showed that selective movement of Na
+
ions into
the cell followed by an efl ux of K
+
ions is the basis for the electrical activity in nerve cells. The
ions move passively across the cell membrane when the permeability increases, and the direction
of the movement is determined by the combined chemical and electrical forces acting on them.
