Smooth and Cardiac muscle

By
Ms Muzanenhamo M.C
Objectives
• Describe cardiac and smooth muscle morphology
• Explain the excitation - contraction mechanisms in cardiac and smooth
muscles
• Describe how an action potential occurs in cardiac and pacemaker
cells/ tissues
• Classify smooth muscles based on functionality
• Discuss the effect of various drugs on cardiac and smooth muscles
Smooth muscle
• Overview
– Have no striations (hence smooth)
– Innervated from autonomic nervous system (involuntary control)
– Wide range of functions (lining hollow organs, to control of eye movement)
– Can be excitatory or inhibitory
– Multiple neurotransmitters
– Use Ca/Actin-Myosin contractile mechanism
– Organisation of contractile proteins/and excitation contraction mechanism is different
Smooth muscle cells
• No striations – no sarcomere, hence no myofibrils
• Contractile proteins anchored to plasma membrane or to dense bodies (similar to Z lines)
• Filaments are diagonal to the length of the muscle, cell is almond shaped
• Single nucleus and can divide
• Generally two types
– Single Unit
• Connected by gap junctions
• One motor neuron innervating many cells
– Multiunit
• One or more motor units innervating a single cell
• Much finer coordination of contraction
• Lengths over which tension can develop is greater – highly adaptive towards aligning hollow organs
Innervation of SM
• It has no NMJ but can have multiple electrical input
• Contractile activity influenced by NTs from autonomic nerve endings
• Axon divides into multiple branches with varicosities (with numerous vesicles)
• Varicosities from a single axon can be located along multiple muscle fibres and a single muscle
fibre can be along varicosities from different axons
• Multiple muscle fibres influenced by one nerve fibre or
• Single muscle fibre influenced by multiple fibres
• Junction is less organised
• Numerous NTs from either sympathetic (Adr) or parasympathetic (ACh) systems (tissue specific )
• NT can be depolarising or hyperpolarising
Smooth muscle contraction Increase in cytosolic calcium
• Thin filaments do not have
calcium binding protein – Calcium binds to calmodulin (calcium
troponin mediating the cross
binding protein whose structure is
bridge activity
related to troponin)
• Cross bridge cycling is
regulated by a calcium regulated
enzyme that phosphorylates Ca2+-calmodullin complex binds to
myosin.
myosin light chain kinase

Myosin light chain kinase uses ATP to

phosphorylate myosin cross bridges (thick filament)

Phosphorylated cross bridges bind to

actin filaments (dephosphorylation myosin light chain
phosphatase)

Cross bridge cycle produces tension

and shortening
Smooth Muscles
• Cross bridge activation is turned on by • Relaxation of smooth muscle due to
Calcium mediated changes in thick dephosphorylation (phosphatase
filaments (compare with skeletal enzyme) of phosphorylated myosin
muscles) • Phosphatase is always present in its
• Smooth muscle myosin isozyme has a active form
very low rate of ATPase activity • Cytosolic calcium has effect on rate of
(important to ensuring fatigue does not myosin phosphorylation
occur)
• As it increases, phosphorylation
exceeds dephosphorylation
Sources and Removal of Ca
• Primarily two sources
• Sarcoplasmic Reticulum (SR)
• Plasma Membrane Calcium Channels
• SR
• No T-Tubules connected to plasma membrane
• Second messengers (IP3) may trigger release from the SR
• Ca Channels
• Voltage gated Ca Channels on the plasma membrane
• Removal of Ca
• Active transport into the SR and out of the cell
• Rate of removal is slower in SM compared to skeletal muscle
• Tension can be GRADED by varying the conc. of cytosolic Ca
Smooth Muscle cntd
• Factors influencing smooth
• Stimulation muscle contractile activity
• Visceral smooth muscle unique in that it contracts •when stretched electrical
Spontaneous in the absence of any
activity
extrinsic innervation (pacemaker potential) • Neurotransmitters released by
the autonomic neurons
• Function of the nerve supply is not to initiate contraction in the muscle but to modify it.
• Hormones
• Locally induced changes in
the ECF surrounding the fiber
• Stretch
Smooth Muscles
• Effect of NA
• NA chemical mediator from noradrenergic nerve endings
• Increases the membrane potential, decreases spontaneous spike potentials
• Relaxes muscle
• Result of increased calcium efflux from the cell. Mediated via cyclic AMP
• Effect of Ach
• Membrane potential decreases,
• Muscle is more active with increase in tonic tension and increase in rhythmic contractions
• Result of increase intracellular calcium conc. Mediated by phospholipase C and IP3
Smooth Muscles
• Local Factors
• Paracrine agents, oxygen conc., osmolarity, ion composition in the ECF affect
smooth muscle tension
• Exact mechanisms are not known
• Stretch
• Opens mechanosensitive ion channels, causing depolarization, muscle
contraction
Difference between smooth & skeletal muscle contraction
Cardiac Muscle
• Features
• Combine characteristics of both skeletal and smooth muscles
• Striations similar to skeletal muscle (sarcomere)
• Have large numbers of mitochondria in close contact with the muscle fibrils
• Muscle fibers branch and interdigitate – each is a complete unit surrounded by a cell
membrane
• Intercalated disks provide strong union between fibers, maintaining cell to cell cohesion such
that the pull of one contractile unit can be transmitted to the next
• Cell membranes of adjacent fibers fuse forming gap junctions – provide low resistance
bridges for the spread of excitation from one fiber to another: enabling the cardiac muscle to
function in syncytium
• The T system in cardiac muscle is located at the Z lines rather than at the A–I junction, where
it is located in skeletal muscle.
• Contains myosin, actin, tropomyosin and troponin
Cardiac Muscle
Innervation
• Has both sympathetic and parasympathetic input
• Sympathetic
• Cardiopulmonary splanchnic nerves
• Neurotransmitter is noradrenaline
• Beta1 subtype of receptors
• Increases HR and Contractility
• Parasympathetic
• Vagus nerve (CN X)
• NT is ACh
• Receptor: muscarinic 2
• Decreases HR and Contractility
• At rest
• Parasympathetic is dominant (vagal control)
 RMP & AP of cardiac muscle
• RMP of mammalian cardiac muscle cells is
~ -90 mV (closer to Keq)
• During an action potential depolarisation (2 ms)
is followed by a plateau (200 ms) before
returning to the baseline
• Changes in the external K concentration
affect the RMP.
• Initial rapid depolarization and overshoot
(phase 0) are due to opening of voltage
gated Na channels.

*Atrial AP has all the phases present in a ventricular action potential. The slight modification is the
reduced plateau or phase 1 and 2. This is due to the reduced density of slow Ca and Na channels in the
atrium.
 RMP & AP of cardiac muscle
• Initial rapid repolarization (phase 1) is due to
closure of Na channels and opening of one type of
K channel

• Prolonged plateau phase (phase 2) is due to a

slower but prolonged opening of voltage gated Ca
channels

• Final repolarization (phase 3) to RMP (phase 4) is

due to closure of Ca channels and a slow, delayed
increase of K efflux through various types of
channels
Conduction System of the Heart
• Pacemaker from SA node, spreads to the AV
node (AV nodal delay 0.1s), spreads via the
interventricular septum (bundle of His),
dividing into left and right bundles, contacting
the Purkinje fibers and then myocardia

Ref: http://emedicine.medscape.com/article/1922987-
overview
Excitation-Contraction Coupling
• Calcium induced calcium release
• AP opens voltage sensitive Ca channels on the plasma membrane
• ECF Ca moves into the cell (slight increase)
• Increase in cytosolic Ca actives larger release of Ca from SR
• Amplification effect on the release of Ca
• Conc. of Ca released determines the strength of contraction
• Contraction ends due to active pumping of Ca out of the cell
Cardiac Muscle AP
• Electrical
Phases of Cardiac
Properties
action potential
• Phase
RMP of0 cardiac
– Rapidmuscles
depolarisation
-90mv (closer to Keq)
• Dueantoaction
During opening of voltage
potential gated sodium channels
depolarisation is followed by a plateau before returning to the baseline
•• Phase 1 –Rapidlasts
Depolarisation repolarisation
about 2ms, plateau and repolarisation last 200ms.
• Due to closure of sodium channels
• Repolarization is therefore not complete until the contraction is half over.
• Phase 2 – Plateau
• Changes
• Due in
to aexternal K+ concentration
slower prolonged opening ofaffect thegated
voltage RMP calcium channel balancing K efflux
•• Changes
Phase 3 –inFinal
external Na concentration affect the magnitude of the action potential
+
repolarisation
• Closure of calcium channels and potassium efflux
• Phase 4 – RMP
K efflux restores the RMP
The Cardiac AP
Refractory Period
• In skeletal muscle a second contraction can be elicited before the first is over(summation of
contractions)
• In cardiac muscle the absolute refractory period lasts about 250ms, inhibiting the muscle from
being re-excited
• The absolute refractory period almost covers the entire duration of the muscle contraction.
Cardiac APs