第一·节 心脏的生物电现象及节律性
兴奋的产生与传导
心肌组织的生理特性：兴奋性 传导性 自律性 收缩性
心肌细胞的分类：
工作细胞（普通心肌）：心房肌细胞，心室肌细胞
自律细胞（特殊传导系统）：起搏（Ｐ）细胞，浦肯野细胞
二种细胞的比较:
兴奋性 传导性 自律性 收缩性
工作细胞
有
有
无
有
自律细胞
有
有
有
无
Electrical Activity of the Heart
OBJECTIVES
• Explain the types of cardiac action potentials.
• Define the ionic basis of cardiac action potentials.
• Explain the temporal changes in cardiac excitability.
• 心肌细胞的快反应动作电位和慢反应动作电位；
• 心肌细胞的电生理特性（传导性和兴奋性）
威廉 . 艾因特霍芬
（Willem Einthoven）
Willem Einthoven
荷兰生理学家 威廉 . 艾因特霍芬
（ Willem Einthoven, 1860~1927 ） 因对
心电图学 的 开创性工作和 无与伦比 的贡
献 而 被誉为“心电图之父”，并于 1924
年获 诺贝尔生理学或医学奖。
Cardiac Transmembrane Potentials are Prolonged
The electrical behavior of
cardiac cells differs considerably
from that of nerve cells or of
smooth or skeletal muscle ceils. in
general, the durations of action
potentials are much longer in
cardiac cells than in nerve cells or
in smooth or skeletal muscle cells.
The action potentials differ
substantially among various
type of cardiac cells depending
on the function and location of
those cells.
the potential charge recorded from ventricular muscle cell
Resting potential ： - 90 mV (interior is lower than
that of the surrounding medium)
Action potential:
Phase 0 : the rapid upstroke of the action potential.
depolarizes from -90mV to +20～30 mV;
Phase 1 ：a brief period of partial
repolarization
+20 mV  0 mV,
Phase 2 ：a plateau ( persists
for about 0.2 second).
It is main difference
comparing with nerve
and skeleton muscle cells.
Phase 3 ：repolarization This proceeds more slowly than
dose depolarization (phase 0).
Phase 4 : The interval from the completion of repolarization
until the beginning of the next action potential.
Action potential occurs well before the contractile force
attains its peak, and repolarization is completed well
before the cell reaches its full resting value. The relaxation
of the cardiac muscle takes place mainly during phase 4 of
the action potential.
There Are Two Principal Types of Cardiac Action
Potentials
• Fast-response action potentials: occur in atrial and
ventricular myocardiac fibers and specialized conducting
fibers (Purkinje fibers) that exist mainly in the
endocardiac surfaces of the ventricles.
• Slow-response action potentials: occur in the sinoatrial
(SA) node (SA), which is the natural pacemaker region of
the heart;
and the atrioventricular (AV) node, which is the
specialized tissue that conducts the cardiac impulse from
the atria to the ventricles.
Comparing with the fast-response action potential:
The resting membrane of slower-response is considerable
less negative, about -50 mV;
The slop of the upstroke (phase 0), the amplitude and
overshoot of the action potentials are less; （amplitude of
action potential and the rate of rise of the upstroke are
important determinants of the conduction velocity).
Fast responses may change to slow responses under
certain pathological conditions, for example, in coronary
artery disease
The Cardiac Transmembrane Potential
Dependends Mainly on K+, Na+, and Ca++
Each phase of the action potential is associated
with a change in conductance to one or more ions.
The Resting Potential Is Determined by Ionic Diffusion
After raising [K]o, the measured value of Vm
approximates that predicated by the Nernst equeation for
Km (equilibrium potential). The measured values are slightly
less negative than those predicted by Nernst equation
because of the small but finite gNa
The Fast Response Depends on Na+
Phase 0 is genesis of the upstroke
Any stimulus that abruptly
changes the resting membrane
potential to a critical value
(called the threshold 阈值)
results in an action potential.
The rapid depolarization
(phase 0) is related almost
exclusively to the influx of Na+
into the myocyte due to a sudden
increase in gNa.
The amplitude of the action
potential (the potential change
during phase 0) varies
linearly with the logarithm of
[Na+]o,
When [Na+]o is increased
from about 20% of its
normal value to about 150%
of its normal value, the
transmembrane potential at
the peak of the action
potential increases from
about -20 mV to about +40
mV.
When the resting membrane potential, Vm, is
suddenly changed from -90 mV to the threshold level
of about -65 mV the properties of the cell membrane
change dramatically.
Na+ enters the myocyte
through specific fast Na+
channels that exist in the
membrane.
These channels can be blocked
by the puffer fish toxin,
tetrodotoxin.
the m gate,
tends to open the channel
as Vm becomes less
negative. Hence, this is
called an activation gate.
the h gate,
close the channel as Vm
becomes less negative.
Hence, this is called an
inactivation gate.
Regenerative
The consequent change in Vm opens more m gates and
augments the inward Na+ current. As Vm approaches about
-65 mV, the remaining m gates rapidly swing open in the fast
Na+ channels until virtually all the m gates are open
Effective refractory period
The h gates then remain closed until the cell has
partially repolarized during phase 3, in this time the
cell is in its effective refractory period, and it will not
respond to further excitation.
Recovered from inactivation
Na+通道有三种状态，都是电压依赖性的：
备用 (-90 mV)  激活  失活
Phase 1 is genesis of early repolarization
Two mechanisms are responsible for phase 1:
• When a notch is not evidence,
phase 1 reflects the
inactivation of the fast Na+
channels.
• In cells characterized by a
notch, phase 1 reflects not only
the inactivation of Na+ channels,
but also activation of a specific
K+ current (transient outward
current [Ito].
Roderick MacKinnon
罗德里克.麦金农
Rockefeller
University,
Howard Hughes
Medical Institute
New York, NY, USA
For inactivation to occur, a positively charged inactivation particle (ball) has to
pass through one of the lateral windows and bind in the hydrophobic binding
pocket of the pore’s central cavity.
Kv1.4, 2001
Phase 2 is genesis of the plateau
• The principal movement of cations across the cell
membrane during phase 2 are a net efflux of K+ and a
net influx of Ca 2+ .
• The relevant Ca2+ channels is Ltype Ca2+ channels. A substantial
amount of Ca2+ enter the cardiac
cells throughout the plateau as
three reasons: gCa2+, Ca 2+
concentration, positive potential.
•
Plateau remains fairly constant
for about 100 to 300 ms.
• Various medications and neurotransmetters may influence the
Ca2+ current in cardiac cells.
• Epinephrine strengthen
myocardial contraction by
increasing Ca2+ influx.
• Ca2+ channels antagonist
diminish the level of Vm during
the plateau and abridge the
duration of plateau by altering the
balance between Ca2+ influx and
K+ efflux.
地尔硫唑
Phase 3 is genesis of final repolarization
• when the efflux of K+ front the cardiac cell begins to
exceed the influx of Ca2+ final repolarization stars.
• At least three outward K+ currents (ito, ik, and ik1)
contribute to the final repolarization (phase 3) of the
cardiac cell.
The Slow Response Is Found in all Cardiac Cells
• fast-response action potentials consist of four
components:
an upstroke (phase 0);
an early, partial repolarization (phase 1);
a plateau (phase 2);
and a final repolarization (phase 3).
• slow response action potentials
the upstroke is much more gradual,
the early repolarization (phase 1) is absent,
the plateau is less prolonged and less flat,
The transition from the plateau to the final repolarization is
less distinct.
• SA and AV nodes are normally slow-response fibers.
In such fibers, depolarization is achieved mainly by the
influx of Ca++ through the Ca++ channels.
• Repolarization is accomplished in these fibers by the
inactivation of the Ca++ channels and by the increased
K+ conductance through the iK1 and iK channels.
The Fast Response Underlies Rapid Conduction of the
Cardiac Impulse
The conduction velocity along the fiber varies directly
with the amplitude of the action potential and with the
rate of change of potential (dVm/dt) during phase 0.
important factor which determine the conduction velocity.
• the amplitude of the action potential,
• the rate of change of potential (dVm/dt) during phase 0,
• The level of the resting membrane potential：This factor
influences the amplitude of the action potential and the
slope of the upstroke.
The Na+ Current Determines Conduction of the Fast Response
The Ca++ Current Determines Conduction of the Slow
Response
The threshold potential is about -40 mV for the slow
response, and this response is much slower than it is
for the fast response. The conduction velocities of the
slow responses in the SA and AV nodes are about 0.02
to 0.1 m/sec.
The fast-response conduction velocities are about 0.3
to 1 m/sec for myocardial cells, and the velocities are
about 1 to 4 m/sec for the specialized conducting
(Purkinje) fibers in the ventricles.
Fast responses may change to slow responses under
certain pathological conditions, for example, in coronary
artery disease。
Cardiac Excitability Is Determined by the Availability
of Na+ and Ca++ Currents
Na+ channel activation and inactivation induced
refractory period （不应期）:
Effective refractory period:（有效不应期）
The internal from the beginning
of the action potential until the
time the fiber can conduct
another action potential.
• from the beginning of phase
0 to the time in phase 3 at
which Vm has reached about
-50 mV (c to d).
• At about this value of Vm, the electrochemical m and h
gates for many of the fast Na+ channels have been reset.
Relatively refractory period: during period (d to e), an
action potential may be evoked but only when the
stimulus is stronger than that which elicits a response
during phase 4.
图4-11 心肌细胞动作电位与兴奋性的变化
A. 在复极化的不同时期给予刺激所引起的反应
（a 为局部反应，b、c 和 d 为 0 期去极化速度和幅度都减小的动作电位）
B. 用阈值变化曲线表示心肌细胞兴奋后兴奋性的变化
Premature systole and compensatory pause
Premature systole (期前收缩):
Compensatory pause (代偿间隙):
Ca++ channel generates the slow response:
post-repolarization refractoriness:
In slow-response fibers, the relative refractory Period
frequently extends well beyond phase 3 . Even after the cell
has completely repolarized, it may be difficult to evoke a
propagated response for some time.
Natural Excitation of the Heart
Objectives
• Discuss the basis of automaticity.
• Describe the spread of excitation of the heart.
• Describe the components of the electrocardiogram
Automaticity: the ability to initiate a heartbeat
Rhythmicity: the frequency and regularity of such
pacemaking activity are intrinsic to cardiac tissue
Natural pacemaker: the natural pacemaker cells are
located in the SA node in the mammalian heart;
Ectopic pacemakers : Other regions of the heart that can
initiate beats under special circumstances are called
ectopic pacemakers.
Ectopic pacemakers may become dominant when
(1) their own rhythmicity is enhanced,
(2) The more rhythmic pacemakers are depressed,
(3) all conduction pathways are blocked.
The Sinoatrial Node Is the Natural Pacemaker of the Heart
In adult humans, the SA node is about 8 mm long and 2 mm
thick, and it lies posteriorly in the groove at the junction
between the superior vena cava and the right atrium
• small, round cells，it are
probably the pacenraker cells.
• slender, elongated cells, which are
probably conduct the impulses to
nodal margins
• transmembrane action potential
of the pacemaker cell in the SA
node are characteristic of the slow
response.
• The principal distinguishing feature of an automatic
fiber in the SA node (as in all automatic fibers) resides in
phase 4.
• The automatic cell in the heart displays a gradual diastolic
depolarization (pacemaker potential) during phase 4.
The firing frequency of an automatic cell is varied by
• changing the slope of the slow diastolic depolarization
• the maximum negativity during phase 4
• the value of the triggering threshold
• Through the release of acetylcholine, increased
parasympathetic activity diminishes the heart rate by
reducing the slope and by increasing the maximum
negativity of slow diastolic depolarization.
• Changes in the firing threshold occur in response to
certain medications and to changes in the ionic
composition of the myocardial interstitial fluid.
fluxes of K+, Ca++ , and Na+ underlie automaticity
In the SA node, the slow diastolic
depolarization is mediated by changes
in at least three ionic currents:
• an inward funny" current (if),
• an inward Ca++ current (iCa),
• an outward K+ current (iK) .
if is carried mainly by Na+.
It is activated as the membrane
potential becomes more negative
than about -50 mV during
repolarization
The more negative the membrane potential, the greater of if .
iCa is activated toward the end of
phase 4 (about -55 mV). The influx
of Ca++ accelerates repolarization,
which quickly leads to the upstroke
of the action potential.
The efflux of K+ tends to
oppose the depolarizing effects
of if and iCa.
The outward current iK decays
steadily throughout phase 4
because of its gradual inactivation.
The diminishing of outward iK thus
contributes to the slow diastolic
depolarization.
• The ionic basis for automaticity in the AV node pacemaker
cells resembles that in the SA node cells.
• For automaticity in
Purkinje fibers, the Ca++
current does not contribute
the slow diastolic
depolarization .
• Hence the slow diastolic
depolarization in Purkinje
fibers is mediated by the
balance between the if (x),
and the gradually
diminishing iK (y)
•.
The properties of automaticity in difference cardiac tissue
SA node > AV node > Purkinje fibers
90~100次/分 40~60次/分
15~40次/分
Overdrive suppresses automaticity
• The automaticity of pacemaker cells is suppressed
temporarily after they have been driven at a critically
high frequency. This phenomenon is known as overdrive
suppression.
• The mechanism responsible for overdrive suppression
involves the membrane pump (Na+-K+-ATPase) . This
enhanced activity of the Na+ pump hyperpolarizes the cell
membrane because there is a net loss of cation from the
cell interior. (sick sinus syndrome )
Atrial Muscle Conducts the Cardiac impulse from
the Sinoatrial Node to the Atrioventricular Node
From the SA node, the cardiac
impulse spreads radially
throughout the right atrium
along ordinary atrial
myocardial fibers, at a
conduction velocity of 1 m/sec.
A special pathway, the anterior
interatrial myocardial band
(Bachmann's bundle), conducts
the impulse from the SA node
directly to the left atrium.
Atrioventricuiar Node Connects the Atria
to the Ventricuiar Conducting System
The AV node in adult human is 22 mm
long, 10 mm wide, and 3 mm thick.
The AV node is divided into the
following functional regions:
(1) the A-N region,
(2) the N region,
(3) the N-H region, in which tile nodal
fibers gradually merge with the bundle of His。
The conduction velocity is actually slower in the N region
than in the AN region the conduction velocity is about 0.05
m/sec.. The principal delay in the passage of the impulse
from the atria to the ventricles occurs in the AN and N
regions of the AV node.
An abnormal prolongation of the AV conduction time is
called first-degree AV block.
Ventricular Conduction is Rapid
• The bundle of His is the beginning
of the specialized conduction system
for the ventricles .
• The right bundle branch, a direct
continuation of the bundle of His,
proceeds down the right side of the
interventricular septum.
• The left bundle branch is thicker
than the right. It arises almost
perpendicularly from the bundle of
His and perforates the
interventricular septum.
The bundle branches ultimately
subdivide into a complex network
of conducting fibers, called
Purkinje fibers, which ramify over
the subendocardial surfaces of
both ventricles .
Purkinje fibers are tile broadest
cells in the heart, 70 to 80 um in
diameter. conduction velocity
are 1 to 4 m/sec.
Electrocardiography Is an Important Clinical Tool
The electrocardiogram enables to infer the course of the
cardiac impulse by recording the variations in electrical
potential at various loci on the surface of the body.
By analyzing the details of these fluctuations, the
physician gains valuable insight concerning:
(1) the anatomical orientation of the heart and the
relative sizes of its chambers;
(2) various disturbances of rhythm and conduction;
(3) the extent, location, and progress of ischemic injury
to the myocardium;
(4) the effects of altered electrolyte concentrations;
(5) the influence of certain medications on the heart.
a lead is the electrical connection
from the patient's skin to the
recording device (an
lectrocardiograph).
The electrocardiogram reflects
the temporal changes in the
electrical potential between pairs
of points on the skin surface.
The cardiac impulse progresses
through the heart in a complex
three-dimensional pattern.
P wave reflects the
depolarization of the atrial
myocardial cells.
The configuration and
amplitude of the QRS complex
vary considerably among
individuals. The duration is
usually between 0.06 and 0.10
second.
The T wave reflects the repolarization of the
ventricular myocardial cells. The T wave is usually
deflected in the same direction from the isoelectric line
as is the major component of the QRS complex.
The PR interval is the time
from the beginning of atrial
activation to the beginning of
ventricular activation;
it normally ranges from 0.12
to 0.20 second. Most of this
conduction time involves the
passage of the impulse
through the AV conduction
system.
During the ST interval, the entire ventricular myocacdium
is depolarized. Because all of the myocardial cells are at
about the same electrical potential, the ST segment lies on
the isoelectric line (which is the line that reflects that
virtually all regions of the cardiac surface are at the same
electrical potential).
The QT interval is
sometimes referred to as the
period of electrical systole of
the ventricles; it reflects the
action potential duration of
the ventricular myocardial
ceils. The duration of the QT
interval is about 0.4 second,
but it varies inversely with
the heart rate, mainly
because the action potential
duration varies inversely
with the heart rate.