CHAPTER 2 • ELECTRICAL ACTIVITY OF THE HEART
15
of ion channels responsible for its movement
across a cell membrane. For example, several
different types of potassium channels exist
through which potassium ions can move
across the cell membrane.
Two general types of ion channels exist:
voltage-gated (voltage-operated) and receptor-
gated
(receptor-operated)
channels.
Voltage-
gated channels open and close in response to
changes in membrane potential. Examples of
voltage-gated channels include several sodium,
potassium,
and
calcium
channels
that
are
involved in cardiac action potentials. Recep-
tor-gated channels open and close in response
to chemical signals operating through mem-
brane receptors. For example, acetylcholine,
which is the neurotransmitter released by the
vagus nerves innervating the heart, binds to a
sarcolemmal receptor that subsequently leads
to the opening of special types of potassium
channels (I
K, ACh
).
Ion channels have both open and closed
states. Ions pass through the channel only
while it is in the open state. The open and
closed
states
of
voltage-gated
channels
are regulated by the membrane potential.
Fast sodium channels have been the most
extensively studied, and a conceptual model
has been developed based upon studies by
Hodgkin and Huxley in the 1950s using the
squid giant axon. In this model, two gates
regulate the movement of sodium through the
channel (Fig. 2.3). At a normal resting mem-
brane potential (about -9 0 mV in cardiac
myocytes), the sodium channel is in a resting,
closed state. In this configuration, the m-gate
(activation gate) is closed and the h-gate
(inactivation gate) is open. These gates are
polypeptides that are part of the transmem-
brane protein channel, and they undergo con-
formational changes in response to changes
in voltage. The m-gates rapidly become acti-
vated and open when the membrane is rap-
idly depolarized. This permits sodium, driven
by its electrochemical gradient, to enter the
cell. As the m-gates open, the h-gates begin
to close; however, the m-gates open more rap-
idly than the h-gates close. The difference in
the opening and closing rates of the two gates
permits sodium to briefly enter the cell. After
a few milliseconds, however, the h-gates close
and sodium ceases to enter the cell. The clos-
ing of the h-gates therefore limits the length
of time that sodium can enter the cell. This
inactivated, closed state persists throughout
the repolarization phase as the membrane
potential recovers to its resting level. Near
the end of repolarization, the negative mem-
brane potential causes the m-gates to close
and the h-gates to open. These changes cause
Na+
outside
inside
Na+
Na+
Na+
n
n
Resting
Activated
Inactivated
(closed)
(open)
(closed)
-----------------►
-----------------------------------
Depolarization
Repolarization
Resting
(closed)
■ FIGURE 2.3 Open and closed states of fast sodium channels in cardiac myocytes. In the resting (closed)
state, the m-gates (activation gates) are closed, although the h-gates (inactivation gates) are open. Rapid
depolarization to threshold opens the m-gates (voltage activated), thereby opening the channel and ena-
bling sodium to enter the cell. Shortly thereafter, as the cell begins to repolarize, the h-gates close and the
channel becomes inactivated. Toward the end of repolarization, the m-gates again close and the h-gates
open. This brings the channel back to its resting state.
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