Excitable tissue- cardiac muscle
Dr. Shafali Singh
Learning Objectives
• Recognize the structure and function of cardiac
muscle( as a syncytium, intercalated disc, gap
junctions) and how it differs from skeletal muscle and
other smooth muscle.
• Describe the characteristics of resting ventricular
muscle cell.
• Describe the Action potential in a cardiac muscle cell
fast response fiber.
• Understand mechanisms underlying contraction,
relaxation, and regulation of the force of contraction of
cardiac muscle cells .
Cardiac muscle: syncytium of myocytes with
intercalated disc and gap junctions
Characteristics of a Resting Ventricular Muscle
Cell
MEMBRANE CHANNELS
Ungated Potassium Channels
• Always open and unless the membrane
potential reaches the potassium equilibrium
potential (~ –94 mV), a potassium efflux is
maintained through these channels.
Voltage-Gated Sodium Channels (fast channels)
• These are closed under resting conditions.
• Membrane depolarization is the signal that
causes these channels to quickly open and then
close.
• These channels have the same characteristics as
the voltage-gated sodium channels in the
neuron axon.
• Once closed, they will not respond to a second
stimulus until the cell repolarizes.
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Voltage-Gated Calcium Channels (slow
channels)
Closed under resting conditions, when the
membrane potential is highly negative.
Depolarization is the signal that causes these
channels to open.
They open more slowly than the sodium
channels.
Consequently, they are sometimes called the
slow channels.
They are also called L-type, for long-acting
channels.
• Because they allow sodium as well as
calcium to pass, they are also called slow
calcium-sodium channels.
• The calcium entering the cell through these
channels will participate in contraction and
will also be involved in the release of
additional calcium from the sarcoplasmic
reticulum.
Voltage-Gated Potassium Channels
• There are several types of voltage-gated potassium
channels, of which two are more important.
Delayed rectifying channels, iK
• Control is more like voltage gated potassium channels in
nerves; the iK channel opens with depolarization and
closes when the cell is repolarized.
• However, they are very slow to open (delayed). They
typically open late in the plateau phase of the action
potential to speed repolarization.
• They close very slowly and thus remain open into the
resting potential and contribute to the extended period of
the relative refractory period.
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Inward rectifying channels, iK1
Open under resting conditions (negative
membrane potentials), depolarization is the
signal to close these channels.
They start closing with depolarization and
remain closed during the main part of the
plateau phase.
They reopen again during repolarization.
Low potassium conductance is extremely
important for the development of plateau
phase.
Q. Which of the following changes would be
expected to make the membrane potential of
a muscle cell more positive than normal
(resting cell)?
A. Increased conductance to calcium
B. Increased conductance to potassium
C. Increased conductance to chloride
D. Decreased conductance to sodium
• the fast response, occurs in normal atrial and
ventricular myocytes and in the specialized
conducting fibers (Purkinje fibers of the heart)
Phases
of
Action
Potent
ial
Ionic Basis of the Action Potential
Phase 0, Upstroke
Phase 1, Early Repolarization
• Fast channels open, ↑ • This slight repolarization is
gNa. Sodium influx
due to a net transient
causes depolarization.
potassium current and the
closing of the sodium
• The channels open and
channels.
close quickly, and they
have closed by the time • Subendocardial fibers lack
the main part of the
phase 1.
plateau phase is
entered.
Phase 2, Plateau
• L-type Ca2+ channels are open, gCa ↑
permitting a calcium influx.
• Voltage-gated potassium channels, the iK1, are
closed; gK ↓ compared with resting membrane.
• Potassium efflux continues through the ungated
potassium channels
• Calcium channel antagonists shorten the plateau.
L-type channels are blocked by Ca++ channel
antagonists such as verapamil, amlodipine, and
diltiazem
• Potassium channel antagonists lengthen the
plateau.
IN THE CLINIC- Ca++ channel antagonists
• Verapamil, Amlodipine, and Diltiazem.
• Decrease gCa and thereby impede the influx of Ca++ into
myocardial cells.
• Decrease the duration of the action potential plateau and
diminish the strength of the cardiac contraction
• Also depress the contraction of vascular smooth muscle
and thereby induce generalized vasodilation. This
diminished vascular resistance reduces the counterforce
(afterload) that opposes the propulsion of blood from the
ventricles into the arterial system.Hence, vasodilator drugs
such as the Ca++ channel antagonists are often referred to
as afterload-reducing drugs
Phase 3, Final Repolarization
• L-type Ca2+ channels close, gCa ↓; this
eliminates any influx through these channels.
• Voltage-gated potassium channels, the delayed
rectifier iK, then the iK1 are opening, gK ↑
leading to a large potassium efflux, and the cell
quickly repolarizes.
• If the voltage-gated potassium channels did not
open, the cell would still repolarize but more
slowly, because of closure of calcium channels
and potassium efflux through the ungated
potassium channels.
Phase 4, Restoration of Ionic Concentrations
• gK high; voltage-gated and ungated potassium
channels open.
• The delayed rectifiers, iK, gradually close but
are responsible for the relative refractory
period during early phase 4 with the cell in
hyperpolarized state.
Which phase is most affected if the voltage
gated Potassium channels (delayed rectifier)
are blocked?
High Calcium conductance is seen in
which of the following phases?
Permeability
Voltage and current
EXCITATION-CONTRACTION
COUPLING
Relaxation
Force of contraction is relatively insensitive to
extracellular Ca2+
A. Cardiac muscle
B. Skeletal muscle
C. Smooth muscle
CONTRACTLITY REGULATION
I. Intracellular Calcium
II.Sympathetic
Activation
III. Preload
Dependence
Pre load/Stretch Limits
Correlation between Muscle Fiber
Length & Tension
Hypertrophy of the heart
• In response to exercise -beneficial, with
improved cardiac performance, increased oxygen
consumption, and normal relaxation
• Chronic pressure overload, -- progress to dilated
cardiac hypertrophy characterized by decreased
contractile ability
• Genetic mutations --familial hypertrophic
cardiomyopathy, in which a mutation in a single
intracellular protein may alter contractile
function and promote a hypertrophic response
V. Energy Source
• < 1 sec ,cardiac mus contraction duration.
• It maintains modest ATP stores that support
short contra and then regenerate these stores
using aerobic pathway when relaxed.
• Limited anaerobic capacity creates high
dependence on O2.
• Prolonged O2 deprivation (min)causes
irreversible hypoxic mus damage and
myocardial infraction.