Smooth Muscle Contraction Flashcards
Describe smooth muscle
Elongated, spindle-shaped cells with tapered ends which may occasionally be bifurcated.
Shorter than skeletal muscle fibres containing only one nucleus which is elongated and centrally located.
Individual muscle fibres are arranged roughly parallel to one another
Where is smooth muscle found?
Smooth muscle surrounds blood vessels, GI tract, bronchial airways
What are the two types of functional smooth muscle in regards to their connectivity?
Unitary, single unit, visceral, phasic
Multiunit, tonic
What is unitary/single unit/visceral/phasic functional smooth muscle?
sheets of electrically coupled cells which acts in unison (a ‘syncytium’ e.g., gut and blood vessels
What is multiunit/tonic functional smooth muscle?
Tissue of discrete bundles of cells which are densely innervated and contract only in response to its innervation (e.g., vas deferens, iris, piloerectors)
Describe the structure of the filaments of smooth muscle
- Contains actin and myosin filaments, however not aligned by Z discs so no visible striations
- Actin and myosin filaments aligned diagonally along long axis of cells
- Filaments anchored at dense bodies (α-actinin-rich) scattered throughout sarcoplasm
- Contractile arrays fixed by intermediate filaments (vimentin and desmin)
What connects contractile arrays to the sarcolemma in smooth muscles?
Dense plaques
What are contractile arrays anchored to in smooth muscle?
The sarcolemma
What connects smooth muscle cells?
focal adhesions (adherens junctions)
Describe the tertiary structure of thick (myosin) filaments
Tertiary structure similar but amino acid sequence different to thin filaments*
Contains 2 myosin heavy chains (MHCs)
And
2 myosin light chains (MLCs)
What* are the 2 myosin heavy chains (MHCs) found in thick (myosin) filaments?
Head (contains ATPase and actin binding site)
Neck regions
What are the 2 myosin light chains (MLCs) found in the thick (myosin) filaments?
Essential light chains
Regulatory light chains or MLC20
Describe the thin (actin) filaments
Two smooth muscle actin(SMA) isoforms
Smooth muscle thin filaments do contain tropomyosin BUT do not contain troponin
Thin filaments associate with 2 other regulatory proteins instead
Mechanism of interaction is different too
How are actin sites exposed in thin (actin) filaments?
Actin sites exposed by interaction of regulatory proteins with high concentrations of Ca2+-calmodulin (CaM) or phosphorylation of proteins by Ca2+-calmodulin dependent protein kinase
What are the two smooth muscle actin(SMA) isoforms?
α SMA, dominant in vascular smooth muscle
γ SMA, largely restricted to the GI tract
What are the 2 regulatory proteins found in thin (actin) filaments but not thick (myosin) filaments?
Caldesmon – is an actin associated myosin ATPase inhibitor
Calponin – also an actin associated myosin ATPase inhibitor
What fulfils the role of the absent T(transverse)-tubules in the sarcoplasmic reticulum in smooth muscle?
Caveolae (flask-shaped sarcolemmal pockets) at the plasma membrane
How does the sarcoplasmic reticulum of smooth muscle differ from that of skeletal muscle?
Sarcoplasmic reticulum not as extensive as in skeletal or cardiac muscle
Ca2+ sequestered in extracellular space near caveoli
How does the intracellular stimulus of smooth muscle contraction differ from that of skeletal muscle?
It doesn’t, it is still an increase in intracellular Ca+ ie same as skeletal muscle.
This can be caused by nerve or hormonal stimulation
How does contraction occur in smooth muscle?
only phosphorylated form of myosin can bind to actin and undergo cross-bridge cycling
What phosphorylates myosin in smooth muscle?
Myosin light chain kinase (MLCK)
How does relaxation occur in smooth muscle?
myosin must be dephosphorylated as dephosphorylated myosin is unable to bind to actin
How is dephosphorylation of myosin mediated in smooth muscle?
by myosin light-chain phosphatase (MLCP)
What are the 6 steps of smooth muscle contraction?
- Initiated by calcium from ECF or SR.
- Calcium binds to calmodulin (instead of troponin as in skeletal muscle)
- Ca-calmodulin-MLCK complex leads to phosphorylation of MLC (requires 1 ATP)
- MLC is part of myosin head
- Phosphorylated myosin head binds to actin and power stroke occurs automatically
- A second ATP is required to release myosin head from actin
Describe the 3 steps of smooth muscle relaxation continuing on from smooth muscle contraction?
- Calcium concentration dips below a critical level due to being pumped out of the cell or into the SR*?(caveoli?)
- Calcium is released from calmodulin
- MLCP removes phosphate from the MLC, causing detachment of the myosin head from the actin filament, causing relaxation
What are the types of factors that help increase the Cai2+ in excitation contraction coupling in smooth muscle?
– 2 sources of Ca2+ contribute to increase in Cai2+
– 3 mechanisms can lead to increase in Cai2+
What are the 2 sources of Ca2+ that contribute to increase in Cai2+ in excitation contraction coupling in smooth muscle?
Sarcoplasmic reticulum (SR)
Cao2+ entering the cell through plasma-membrane Ca2+ channels
What are the 3 mechanisms can lead to increase in Cai2+ in excitation contraction coupling in smooth muscle?
– Voltage-gated L-type Ca2+channels (Cav) leading to Calcium-induced calcium release (CICR) via Ryanodine (RYR) receptor activation
– Receptor-operated Ca2+ channels (ROCCs) leading to IP3 receptor activation amd calcium release
– Store operated Ca2+ channels (SOCs)
What allows smooth muscle to maintain high force for long periods?
The formation of latchbridges
unique and fundamental to smooth muscle
What are latchbridges?
A position in which the myosin head is held that allows for contraction over long periods of time and uses minimal ATP due to an intrinsically slow cycling rate
Occurs when myosin is dephosphorylated while still attached to actin (“latches” in place)
What are required for latchbridges to occur?
Latchbridges are contractile events - can only occur if intracellular Ca2+levels remain elevated above background
Where do the Ca2+ ions go in relaxation of smooth muscle cells?
- Ca2+ removed either to the SR or back to the extracellular fluid
variable amounts of Ca2+may be extruded from the cell
How is Ca2+ transported in relaxation of smooth muscle cells?
Ca2+ ATPase (SERCA)
Na+- Ca2+ exchangers
How does the sarcoplasmic reticulum refill its Ca2+ stores in relaxation of smooth muscle?
SR containstore-operated Ca2+channel(SOCs)
These refill SR stores
occurs at specialized regions where SR encounters the sarcolemma
When do store-operated Ca2+channels(SOCs) open?
Store depletion is sensed byStim1, which signals toOrai
SOCs then open leading to Ca influx
What may regulate the contractile activity of a smooth muscle cell?
- Spontaneous electrical activity in muscle cell
- Stretch
- Neurotransmitter released by autonomic neurons
- Hormones
- Locally induced changes in chemical composition (paracrine factors, acidity, oxygen, osmolarity, ion concentrations) of extracellular fluid around myocytes
What is the pacemaker potential?
pacemaker potential is the slow, positive increase in voltage across the cell’s membrane (the membrane potential) that occurs between the end of one action potential and the beginning of the next action potential
Discuss spontaneous electrical activity in the smooth muscle
Some smooth muscle cells generate action potentials spontaneously in the absence of any neural or hormonal input
Membrane potential change during spontaneous depolarization to threshold - pacemaker potential
Some smooth muscle cells have a different pattern of activity
Membrane potential drifts up and down – these periodic fluctuations are called slow waves
Where are pacemaker cells found in smooth muscle and what is their purpose?
Pacemaker cells are found throughout the gastrointestinal tract, and thus gut smooth muscle tends to contract rhythmically even in the absence of neural input
Where do the synapses occur in smooth muscle?
swollen regions known as varicosities;
Unlike skeletal muscle fibers, smooth muscle cells do not have a specialized motor end-plate region
Discuss varicosities
Varicosities contain neurotransmitter filled vesicles
Varicosities from a single axon may be located along several muscle cells
Varicosities originate from postganglionic fibers of both sympathetic and parasympathetic neurons
Several smooth muscle cells are influenced by neurotransmitters released by a single neuron, and a single smooth muscle cell may be influenced by neurotransmitters from more than one neuron
Are neurotransmitters responsible for stimulating contractile activity in smooth muscle?
Yes, but others also decrease contractile activity
Sometimes the same neurotransmitter may have opposite effects on different types of small tissue
What does noradrenalin do in smooth muscle?
just an example
noradrenaline released from postganglionic sympathetic neurons
Stimulates contraction of most vascular smooth muscle by acting on α-adrenergic receptors but produces relaxation of airway (bronchiolar) smooth muscle by acting on β2-adrenergic receptors
What does the response to a neurotransmitter signal depend on?
Type of response (excitatory or inhibitory) depends not on the chemical messenger per se, but on the receptors the chemical messenger binds to in the membrane
What local factors help mediate smooth muscle?
Paracrine signals, acidity, O2 and CO2 levels, osmolarity, ion composition of the extracellular fluid, can all alter smooth muscle tension
Allows for alteration of smooth muscle contraction in response to changes in environment – ‘fine tuning’
Many local factors induce smooth muscle relaxation
Nitric oxide (NO) produces smooth muscle relaxation acting in a paracrine manner
Some smooth muscles respond to stretch by contracting
Activates mechanosensitive (stretch-activated) ion channels leading to membrane depolarization
Resulting contraction opposes the forces acting to stretch the muscle
What activates myosin light chain. kinase (MLCK)?
Calmodulin
Where are the filaments of of smooth muscle anchored?
at alpha actinin rich dense bodies scattered throughout the sarcroplasm
What fixes contractile arrays in smooth muscle?
Intermediate filaments (Vimentin and desmin)
