Biomedical Engineering Reference
In-Depth Information
[Figure 3.5(d)]. Amplifiers are required to increase signal strength while maintain-
ing high fidelity. Although there are many types of electronic amplifiers for different
applications,
operational amplifiers
(normally referred to as
op-amps
), are the most
widely used devices. They are called operational amplifiers because they are used to
perform arithmetic operations (addition, subtraction, multiplication) with signals.
Op-amps are also used to integrate (calculate the areas under) and differentiate
(calculate the slopes of) signals. An op-amp is a DC-coupled high-gain electronic
voltage amplifier with differential inputs (usually two inputs) and, usually, a single
output.
Gain
is the term used for the amount of increased signal level (i.e., the out-
put level divided by the input level). In its ordinary usage, the output of the op-amp
is controlled by negative feedback, which almost completely determines the output
voltage for any given input due to amplifier's high gain. Modern designs of op-amps
are electronically more rugged and normally implemented as integrated circuits. For
complete discussion about op-amps, the reader should refer to textbooks related to
electrical circuits.
One technique to measure electrical activity across a cell membrane is the
space
clamp technique
, where a long thin electrode is inserted into the axon (just like in-
serting a wire into a tube). Injected current is uniformly distributed over the inves-
tigated space of the cell. After exciting the cell by a stimulus, the whole membrane
participates in one membrane action potential, which is different from the propa-
gating action potentials observed physiologically, but describes the phenomenon in
sufficient detail. However, cells without a long axon cannot be space-clamped with
an internal longitudinal electrode, and some spatial and temporal nonuniformity
exists.
Alternatively, the membrane potential is clamped (or set) to a specific value by
inserting an electrode into the axon and applying a sufficient current to it. This is
called the
voltage clamp technique,
the experimental setup used by Hodgkin and
Huxley [Figure 3.5(d)]
.
Since the voltage is fixed, (3.24) simplifies to
(
)
(
)
(
)
I
−ΔΦ −
V
g
−ΔΦ −
V
g
−ΔΦ −
V
g
=
0
inj
m
N
2
N
2
m
K
K
m
leak
leak
American biophysicist Kenneth S. Cole in the 1940s developed the
voltage
clamp
technique using two fine wires twisted around an insulating rod. This meth-
od measures the membrane potential with a microelectrode (discussed in Chapter
9) placed inside the cell, and electronically compares this voltage to the voltage
to be maintained (called the command voltage). The clamp circuitry then passes
a current back into the cell though another intracellular electrode. This electronic
feedback circuit holds the membrane potential at the desired level, even when the
permeability changes that would normally alter the membrane potential (such as
those generated during the action potential). There are different versions of volt-
age clamp experiments. Most importantly, the voltage clamp allows the separation
of membrane ionic and capacitative currents. Therefore, the voltage clamp tech-
nique indicates how membrane potential influences ionic current flow across the
membrane with each individual ionic current. Also, it is much easier to obtain in-
formation about channel behavior using currents measured from an area of mem-
brane with a uniform, controlled voltage, than when the voltage is changing freely
with time and between different regions of membrane. This is especially so as the
