Download Mammalian Physiological Overview of the Heart

Mammalian Physiological
(Bio 440)
Overview of the Heart
-Fundamentals of the cardiovascular system
-Compare skeletal, cardiac and smooth muscle with
respect to histology and neurogenic vs. myogenic
activity.
-Fundamentals of the circulatory system
Neurogenic – extrinsic initiation of muscle activity
Myogenic – intrinsic initiation of muscle activity
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Mammalian Physiological
(Fundamentals)
1) The heart sits at the center of the universe
why? Because I am a cardiovascular
physiologist!
2) The mammalian heart has four chambers
2 – ventricles and 2 – atria
3) The right and left hearts are separate and
distinct with unique circulations and pressures
4) Their flows, however, must be equal! Why?
5) Anatomical and histological design of the
heart and circulatory system.
6) Cardiac cycle
7) Vascular dynamics and regulation
Mammalian Physiological
(Fundamentals)
1) The heart sits at the center of the universe
why? Because I am a cardiovascular
physiologist!
2) The mammalian heart has four chambers
2 – ventricles and 2 – atria
3) The right and left hearts are separate and
distinct with unique circulations and pressures
4) Their flows, however, must be equal! Why?
5) Anatomical and histological design of the
heart and circulatory system.
6) Cardiac cycle
7) Vascular dynamics and regulation
Mammalian Physiological
(Fundamentals)
Mammalian Physiological
(Fundamentals)
1) The heart sits at the center of the universe
why? Because I am a cardiovascular
physiologist!
2) The mammalian heart has four chambers
2 – ventricles and 2 – atria
3) The right and left hearts are separate and
distinct with unique circulations and pressures
4) Their flows, however, must be equal! Why?
5) Anatomical and histological design of the
heart and circulatory system.
6) Cardiac cycle
7) Vascular dynamics and regulation
Systemic circuit
Pulmonary circuit
Mammalian Physiological
(Fundamentals)
1) The heart sits at the center of the universe
why? Because I am a cardiovascular
physiologist!
2) The mammalian heart has four chambers
2 – ventricles and 2 – atria
3) The right and left hearts are separate and
distinct with unique circulations and pressures
4) Their flows, however, must be equal! Why?
5) Anatomical and histological design of the
heart and circulatory system.
6) Cardiac cycle
7) Vascular dynamics and regulation
Mammalian Physiological
(Fundamentals)
1) The heart sits at the center of the universe
why? Because I am a cardiovascular
physiologist!
2) The mammalian heart has four chambers
2 – ventricles and 2 – atria
3) The right and left hearts are separate and
distinct with unique circulations and pressures
4) Their flows, however, must be equal! Why?
5) Anatomical and histological design of the
heart and circulatory system.
6) Cardiac cycle
7) Vascular dynamics and regulation
Mammalian Physiological
(Fundamentals)
1) The heart sits at the center of the universe
why? Because I am a cardiovascular
physiologist!
2) The mammalian heart has four chambers
2 – ventricles and 2 – atria
3) The right and left hearts are separate and
distinct with unique circulations and pressures
4) Their flows, however, must be equal! Why?
5) Anatomical and histological design of the
heart and circulatory system.
6) Cardiac cycle
7) Vascular dynamics and regulation
Mammalian Physiological
(Fundamentals)
1) The heart sits at the center of the universe
why? Because I am a cardiovascular
physiologist!
2) The mammalian heart has four chambers
2 – ventricles and 2 – atria
3) The right and left hearts are separate and
distinct with unique circulations and pressures
4) Their flows, however, must be equal! Why?
5) Anatomical and histological design of the
heart and circulatory system.
6) Cardiac cycle
7) Vascular dynamics and regulation
Mammalian Physiological
(Fundamentals)
1) The heart sits at the center of the universe
why? Because I am a cardiovascular
physiologist!
2) The mammalian heart has four chambers
2 – ventricles and 2 – atria
3) The right and left hearts are separate and
distinct with unique circulations and pressures
4) Their flows, however, must be equal! Why?
5) Anatomical and histological design of the
heart and circulatory system.
6) Cardiac cycle
7) Vascular dynamics and regulation
Mammalian Physiological
(Fundamentals)
1) The heart sits at the center of the universe
why? Because I am a cardiovascular
physiologist!
2) The mammalian heart has four chambers
2 – ventricles and 2 – atria
3) The right and left hearts are separate and
distinct with unique circulations and pressures
4) Their flows, however, must be equal! Why?
5) Anatomical and histological design of the
heart and circulatory system.
6) Cardiac cycle
7) Vascular dynamics and regulation
Mammalian Physiological
(Fundamentals)
1) The heart sits at the center of the universe
why? Because I am a cardiovascular
physiologist!
2) The mammalian heart has four chambers
2 – ventricles and 2 – atria
3) The right and left hearts are separate and
distinct with unique circulations and pressures
4) Their flows, however, must be equal! Why?
5) Anatomical and histological design of the
heart and circulatory system.
6) Cardiac cycle
7) Vascular dynamics and regulation
Mammalian Physiological
(Fundamentals)
1) The heart sits at the center of the universe
why? Because I am a cardiovascular
physiologist!
2) The mammalian heart has four chambers
2 – ventricles and 2 – atria
3) The right and left hearts are separate and
distinct with unique circulations and pressures
4) Their flows, however, must be equal! Why?
5) Anatomical and histological design of the
heart and circulatory system.
6) Cardiac cycle
7) Vascular dynamics and regulation
The Heart Muscle: The heart as a pump
(Moving blood)
Neurogenic Muscle: Contracts in response
to direct nervous input or stimulation via neurohormones.
Skeletal Muscle
Smooth Muscle
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Neurogenic Muscle
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E-C coupling –
excitation-contraction
coupling
The Heart as a Muscle
2 - Action Potentials in Cardiac
Muscle
1 - Myocardial Syncytium
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3 - Excitation-Contraction Coupling
How does the Heart know to
Contract?
Automaticity of pacemaker cells,
Conducting system of the heart and
Myocardium
Myogenic Muscle: Contracts spontaneously
Standard Skeletal Muscle
(Neurogenic)
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1 - Myocardial Syncytium
Myocardial Syncytium
(Functional syncytium)
Cardiac Tissues
-Heart is composed of several types of tissue:
Epithelial
– covers and lines the heart
(epicardium, endocardium)
Connective Tissue - covers the heart as pericardium and
acts as cardiac skeleton
Muscle
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-contractile tissue, myocardium
(myocytes), conducting system of the
heart
Myocardial Syncytium
(Functional syncytium)
Myocardium (contractile tissue)
-Cardiac muscle cells differ from skeletal muscle cells:
shorter (smaller cells)
single or double nuclei
intercalated discs
gap junctions
-Cardiac muscle cells are similar to skeletal muscle cells:
sarcolemma
contractile mechanism similar
T-tubules
SR
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Myocardial Syncytium
(Functional syncytium)
Functioanl syncytium:
-2 functional syncytia:
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-atrial & ventricular
-separated by fibrous CT
-connected by A-V bundle
Myocardial Syncytium
(Functional syncytium)
Distinct electrical signatures
-Slow response potentials
-Fast response potentials
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Cardiac Action Potentials
Cardiac Action
Potentials
1 - Slow response
-sinoatrial node (SA)
-atrioventricular node (AV)
2 - Fast response
-atrial myocytes
-ventricular myocytes
-Purkinje fibers
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Note: (1) fast response resting potential more
Negative. (2) slope of phase 0. (2) amplitude.
(3) overshoot all greater than slow response.
Cardiac Action Potentials
Cardiac Action
Potentials
1 - Slow response
-sinoatrial node (SA)
-atrioventricular node (AV)
2 - Fast response
-atrial myocytes
-ventricular myocytes
-Purkinje fibers
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Note: (1) fast response resting potential more
Negative. (2) slope of phase 0. (2) amplitude.
(3) overshoot all greater than slow response.
Cardiac Action Potentials
(The basics)
Millivolts
1
2
2
0
0
3
0
4
4
-80
(a)
(b)
Fast response
(a)
Slow response
Time (msec)
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(b)
(a) Effective refractory period
(b) Relative refractory period
Fast Response Action Potentials
Phase 0:
1
-resting membrane potential to a critical value
(threshold)
-fast Na+ channels opening (tetrodotoxin blocks)
-regulated by 2 types of gates
-activation gates (m gate) opens when less negative (0.1 msec)
-inactivation gates (h gates) close when more negative (few msec)
-h gates remain closed until the cell has partially repolarized
(phase 3) = Effective refractory period
2
0
4
-Effective refractory period cell will not respond to
further excitation
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-prevents sustained, tetanic contraction which would retard
ventricular relaxation and interfere with normal pumping
-midway through phase 3 – m and h gates have resumed
their initial state (recovered from inactivation)
Fast Response Action Potentials
Phase 1:
1
-early, brief period of limited repolarization
-transient outward current (carried by K+)
-phase 1 seen best in ventricular Purkinje fibers
2
0
4
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Fast Response Action Potentials
Phase 2:
1
2
0
4
-plateau of the action potential
-the result of Ca2+ entry into myocardial cells
through “calcium channels”, voltage regulated
-activate and inactivate more slowly than fast Na+
channels
-influx of Ca2+ counterbalanced by efflux of K+
-K+ close - Inward rectifying current, delayed rectifier
-L-type Ca2+ channels
-inactivates slowly – current “L”ong lasting
*the influx of Ca2+ during the plateau phase is
involved in excitation-contraction coupling
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Fast Response Action Potentials
Phase 2:
1
-Calcium conductance gCa influenced by many
drugs etc.
-norepinephrine – adrenergic neurotransmitter
-isoproterenol – Β-adrenergic receptor agonist
-catecholamines
2
0
4
-Β-adrenergic receptors
-stimulates membrane bound adenylyl cyclase
-increases intracellular cAMP
-enhances activation of L-type Ca2+ channels
-acetylcholine
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-muscarinic receptors
-inhibit adenylyl cyclase
-antagonize activation of Ca2+ channels
Fast Response Action Potentials
Phase 2:
1
2
0
4
-Calcium channel antagonists substances that
block Ca2+ channels
-verapamil
-decrease calcium conductance thus impeding the
influx of Ca2+ into the myocardial cells
-decrease duration of the action potential plateau
-diminish strength of cardiac contraction
-after-load reducing drugs – reduce vascular
smooth muscle contraction (vasodilation)
-reduce resistance
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Fast Response Action Potentials
Phase 3:
1
2
0
4
Phase 4:
-repolarization
-efflux of K+ exceeds the influx of Ca2+
-initiate repolarization and determine the duration of
the plateau phase (outward K+ currents)
-transient outward current
-delayed rectifier current* responsible for
variability in different cell types
-greater the K+ current during plateau phase 2 the
the earlier repolarization begins (atrial myocytes)
-excess Na+ that enters during phase 0 is eliminated
by Na+/K+-ATPase (3Na+ out for 2K+ in)
-excess Ca2+ by Na+/Ca2+ exchanger
(3Na+ in for 1Ca2+ out) and Ca2+ ATP pump
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Slow Response Action Potentials
Phase 1:
Phase 2:
Phase 3:
Phase 3-4:
-upstroke much less steep
-absent
-less prolonged and not as flat
-transition from plateau to repolarization less distinct
SA and AV nodes - depolarization is primarily due to influx of Ca2+
through Ca2+ channels
- repolarization is due to inactivation of Ca2+
channels and increased K+ conductance
2
0
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3
4
Excitation of the heart
Automaticity -ability to initiate its own beat
Rhythmicity -regularity of pacemaking activity
Sinoatrial node – greatest frequency
Thus it is the primary pacemaker
(atrial pacemaker complex)
-8X2 mm
-small round cells* and slender elongated
cells
Cells of the AV junction can also act as
a pacemaker under aberrant conditions
(0)
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(4)
(3)
Excitation of the heart
Automaticity -ability to initiate its own beat
Rhythmicity -regularity of pacemaking activity
Sinoatrial node – greatest frequency
Thus it is the primary pacemaker
(atrial pacemaker complex)
-8X2 mm
-small round cells* and slender elongated
cells
Cells of the AV junction can also act as
a pacemaker under aberrant conditions
(0)
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(4)
(3)
Sinoatrial Node
Phase 4:
-much less negative in SA nodal automatic cells
than in atrial or ventricular myocytes due to
K+ channels are few in number in nodal cells
-phase 4 the potential does not remain constant
-pacemaker fibers show a slow diastolic
depolarization throughout phase 4
-depolarization proceeds at a steady rate until
threshold is attained triggering an action potential
-frequency dependent on:
(1) rate of depolarization during phase 4
(2) the maximal negativity during phase 4
(3) the threshold potential
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Sinoatrial Node
Ionic basis of automaticity:
-Slow diastolic depolarization
1 - inward current if
-”funny” current carried by Na+
-activated by greater –50 mV potential
2 – Ca2+ current iCa
-activated toward end of phase 4 –55mV
-calcium channel activation - influx of Ca2+
-accelerates rate of depolarization
3 – outward current iK
-opposed by this current
-delayed rectifier K+
-efflux of K+
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Autonomic neurotransmitters
Automaticity
Sympathetic and Parasympathetic Nervous systems:
Norepinephrine – raise heart rate by increasing the
slope of the slow diastolic
depolarization (all three currents)
Vagal activity – decreases heart rate
- acetylcholine hyperpolarizes the
pacemaker cells reducing the slope
of the slow diastolic depolarization
(increase in gK – acetylcholineregulated K+ channels)
(depresses if and iCa currents)
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Autonomic neurotransmitters
Automaticity
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Electrocardiography
(The basics)
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