2. Cardiac muscle
• Cardiac muscle, like skeletal muscle, is striated and uses the actin-
myosin-tropomyosin-troponin system
• Unlike skeletal muscle, cardiac muscle exhibits intrinsic rhythmicity,
and individual myocytes communicate with each other because of its
syncytial nature
3. • The T tubular system is more
developed in cardiac muscle
• sarcoplasmic reticulum is less
extensive and consequently the
intracellular supply of Ca2+ for
contraction is less.
• Cardiac muscle relies on
extracellular Ca2+ for contraction
• if isolated cardiac muscle is
deprived of Ca2+, it ceases to beat
within approximately 1 minute,
whereas skeletal muscle can
continue to contract without an
extracellular source of Ca2+.
4. • Cyclic AMP plays a more prominent
role in cardiac than in skeletal
muscle.
• It modulates intracellular levels of
Ca2+ through the activation of
protein kinases; these enzymes
phosphorylate various transport
proteins in the sarcolemma and
sarcoplasmic reticulum and also in
the troponin-tropomyosin
regulatory complex
• This may account for the inotropic
effects (increased contractility) of
β-adrenergic compounds on the
heart
5. General Properties of Ion Channels
• Cardiac electrical activity starts by
the spontaneous excitation of
“pacemaker” cells in the sinoatrial
node (SAN) in the right atrium.
• By traveling through intercellular
gap junctions, the excitation wave
depolarizes adjacent atrial
myocytes, ultimately resulting in
excitation of the atria.
• Next, the excitation wave
propagates the atrioventricular
node (AVN) and the Purkinje via
fibers to the ventricles, where
ventricular myocytes are
depolarized, resulting in excitation
of the ventricles.
6.
7. • Action potential formation results from the opening and closing (gating)
of ion channels that are expressed within the sarcolemma of
cardiomyocytes.
• The direction of ion currents (into the cell [inward] or out of the cell
[outward]) is determined by the electrochemical gradient of the
corresponding ions.
8. • Ion channels have 2 fundamental properties, ion permeation and
gating.
• Ion permeation describes the movement through the open channel.
The selective permeability of ion channels to specific ions is a basis
of classification of ion channels (eg, Na+, K+, and Ca2+ channels).
9.
10. • Gating is the mechanism of
opening and closing of ion
channels and is their second
major property.
• Ion channels are also
subclassified by their
mechanism of gating:
voltage-dependent, ligand-
dependent, and mechano-
sensitive gating.
11. Voltage-gated ion channels
• Voltage-gated ion channels
change their conductance in
response to variations in
membrane potential.
• Voltage-dependent gating is
the commonest mechanism
of gating observed in ion
channels. A majority of ion
channels open in response to
depolarization.
12. Ligand-dependent gating
• Ligand-dependent gating is the
second major gating mechanism
of cardiac ion channels.
• The most thoroughly studied
channel of this class is the
acetylcholine (Ach)-activated K+
channel.
• Acetylcholine binds to the M-2
muscarinic receptor and activates
a G protein–signaling pathway,
culminating in the release of the
subunits Gαi .
13. The mechanosensitive or stretch-activated
channels
• The mechanosensitive or
stretch-activated channels are
the least studied. They belong to
a class of ion channels that can
transduce a physical input such
as stretch into an electric signal
through a change in channel
conductance.
• Acute cardiac dilatation is a
well-recognized cause of cardiac
arrhythmias. Stretch-activated
channel are central to the
mechanism of these
arrhythmias.
14. • The sodium channel consists of 4
homologous domains.
• Each domain consists of 6 membrane-
spanning segments, S1 through S6.
• The membrane-spanning segments
are joined by alternating intra- and
extracellular loops.
• The loops between S5 and S6 of each
domain termed the P loops curve
back into the membrane to form the
pore.
• Each S4 segment has a positively
charged amino acid at every third or
fourth position and acts as the sensor
of the transmembrane voltage.
Sodium Channels
15.
16. • Voltage-gated sodium (Na) channels are transmembrane proteins
responsible for the rapid upstroke of the cardiac action potential, and
for rapid impulse conduction through cardiac tissue.
• Each sodium channel opens very briefly (<1 ms).
• The cardiac sodium channel has consensus sites for phosphorylation
by protein kinase (PKA), protein kinase C (PKC), and Ca-calmodulin
kinase.
17. Calcium Channels
• Calcium ions are the
principal intracellular
signaling ions.
• They regulate excitation–
contraction coupling,
secretion, and the activity of
many enzymes and ion
channels.
18. • In cardiac muscle, 2 types of Ca2+ channels:
• The L- (low threshold type) and T-type (transient-type), transport
Ca2+ into the cells.
• The L-type channel is found in all cardiac cell types.
• The T-type channel is found principally in pacemaker, atrial, and
Purkinje cells.
19. L type calcium channel
• The major portal of entry is the L-type
(long-duration current, large
conductance, also known as the
dihydropyridine channel, or DHP channel)
or slow Ca2+ channel, which is voltage-
gated, opening during depolarization
induced by spread of the cardiac action
potential and closing when the action
potential declines.
• Slow Ca2+ channels are regulated by
cAMP-dependent protein kinases
(stimulatory) and cGMP-protein kinases
(inhibitory) and are blocked by so-called
calcium channel blockers (eg, verapamil)
20. T type calcium channel
• Fast (or T, transient) Ca2+ channels are also present in the
plasmalemma, though in much lower numbers
• they probably contribute to the early phase of increase of myoplasmic
Ca2+.
21.
22. • The resultant increase of Ca2+
in the myoplasm acts on the
Ca2+ release channel of the
sarcoplasmic reticulum to open
it.
• This is called Ca2+-induced
Ca2+ release (CICR).
• It is estimated that
approximately 10% of the Ca2+
involved in contraction enters
the cytosol from the
extracellular fluid and 90%
from the sarcoplasmic
reticulum
23. Ca2+/Na+ EXCHANGER
• This is the principal route of exit of Ca2+ from myocytes.
• In resting myocytes, it helps to maintain a low level of free
intracellular Ca2+ by exchanging one Ca2+ for three Na+.
• This exchange contributes to relaxation but may run in the reverse
direction during excitation. Because of the Ca2+/Na+ exchanger,
anything that causes intracellular Na+ (Na+ i) to rise will secondarily
cause Ca2+i to rise, causing more forceful contraction. This is referred
to as a positive inotropic effect.
24. • One example is when the
drug digitalis is used to treat
heart failure.
• Digitalis inhibits the
sarcolemmal Na+-K+ ATPase,
diminishing exit of Na+ and
thus increasing Na+ i.
• This in turn causes Ca2+ to
increase, via the Ca2+-Na+
exchanger.
• The increased Ca2+i results in
increased force of cardiac
contraction, of benefit in
heart failure
25. Ca2+ ATPASE
• The Ca2+ ATPase of
sarcoplasmic reticulum has a
prominent role in
excitation/contraction coupling
of cardiac muscle, as it induces
relaxation by sequestering
Ca2+ from the cytoplasm.
• The stored Ca2+ is in turn
released to trigger contraction
26. Potasium Channels
• Cardiac K+ channels fall into 3 broad categories: Voltage-gated, inward rectifier
channels, and the background K+ currents.
• It is the variation in the level of expression of these channels that account for regional
differences of the action potential configuration in the atria, ventricles, and across the
myocardial wall.
• K+ channels are also highly regulated and are the basis for the change in action
potential configuration in response to variation in heart rate.
30. Mechanism Of Muscle Contraction
• Step 1. Nerve impulse, travels towards
the synapse.
•Step 2. Ca2+ ion from ECF enter into the
synapse through calcium channels.
31. Mechanism Of Muscle Contraction
•Step 3. As Ca2+ enter into synaptic
knob, Ach. Vesicles ruptures and Ach.
release out into synaptic cleft by
exocytosis.
32. Mechanism Of Muscle Contraction
•Step 4. Ach diffuses across the
neuromuscular junction and binds
to the receptor sites on postsynaptic
membrane.
34. Mechanism Of Muscle Contraction
•Step 5. Stimulating of the receptor
causes conformational change in post
synaptic membrane and generate an
action potential.
Ach (acetylcholine). destroyed by an
enzyme (acetylcholinestrase)
35. Mechanism Of Muscle Contraction
•Step 6. This action potential travels
along the length of muscle fiber, and
then penetrates deep into the muscle
through the T-tubular system.
36. Mechanism Of Muscle Contraction
•Step 7. The electrical impulse
stimulates the sarcoplasmic
reticulum to release calcium into the
(a contractile unit of a mofibril) area.
37. Mechanism Of Muscle Contraction
• Muscle contraction occurs when
calcium is pumped back into the
sarcoplasmic reticulum, away from the
actin and myosin.
• When Calcium moves in this way, the
actin and myosin cannot interact, and
the muscle relaxes.
46. control of cardiac pumping
• Contraction of heart muscle is spontaneous, requiring no external
neurological or hormonal signal but initiated by so-called ‘pacemaker
cells'.
• However, control of cardiac pumping allowing adaptation to the
circumstances is achieved via neural pathways.
47.
48.
49.
50. An Electrocardiogram Is a Record of the
Heartbeat
An electrocardiogram (ECG or
EKG) records the electrical
signal from your heart to
check for different heart
conditions. Electrodes are
placed on your chest to record
your heart's electrical signals,
which cause your heart to
beat. The signals are shown as
waves on an attached
computer monitor or printe
51. • Normal range 120 – 200
ms (3 – 5 small squares
on ECG paper). QRS
duration (measured from
first deflection of QRS
complex to end of QRS
complex at isoelectric
line). Normal range up to
120 ms (3 small squares
on ECG paper).
