2 - Smooth Muscle Flashcards
Type of Smooth Muscle
Non-striated muscle found mostly in hollow organs and tubes
How do contractions compare to skeletal muscles?
Arrangement
Purpose
Contraction Time
Arrangement - Contractile fibers not arranged in sarcomeres
Purpose - Alters dimension of the organ (tube, etc.)
Time - Contractions last much longer than in skeletal muscle
Types of Smooth Muscle: Unitary/Visceral
Organization
Connections
Org: Large sheets
Connected: Gap Junctions, in syncytial fashion–stimulation leads to stimulation of adjacent cells resulting in wave of contraction
Types of Smooth Muscle: Multi-Unit
Organization/Connection
Cells not electrically connected–each cell must be individually stimulated
Actin and Myosin in smooth muscle cells?
Filaments longer than in skeletal muscle
Arranged around periphery of cells
Less myosin than in skeletal muscle
What do actin thin filaments contain in smooth muscle cells?
Tropomyosin, but not troponin
What is unique about the myosin in smooth muscle cells?
Myosin isoform different from skeletal muscle–slower ATPase activity
Sarcoplasmic Reticulum in smooth muscles?
Present, but not T-tubules
Role of Ca2+ in Smooth Muscle:
Increase of intracellular Ca2+
How does it enter into the cell?
How is it released?
Why is it important to have these methods?
Initiates contraction
Enters via voltage-gatedandligand-gated Ca2+ channels
IP3 Channel - activated by IP3 generated from GPCRs; also released from Sarcoplasmic Reticulum (SR)
- - -
Sustained contraction requires extracellular Ca2+ –calcium in = contract, calcium out = relax
Smooth Muscle Actin-Myosin Interactions and Differences w/Skeletal Muscle
(Steps to Drive Contraction)
- Calcium binds to Calmodulin
- Ca-Calmodulin Complex activates myosin light chain kinase (MLCK)
3. MLCK phosphorylates regulatory Light Chains of Myosin (MLC)
- Increases Myosin ATPase activity and binding to actin
Ryanodine Receptor (RYR3) in Smooth Muscle
Present in Smooth Muscle SR
Increase in intracellular Ca2+ activates RYR3
Mechanism of Cross Bridge cycling for smooth muscle?
Same as skeletal muscle
- ATPase on Globilar head of myosin hydrolyzes ATP to ADP and Pi
- Myosin head binds to actin
- Release of ADP and Pi causes myosin head ratchet movement
- ATP binds myosin, actin released
- Will continue as long as MLC phosphorylated and [Ca2+] is high enough
How does kinetics cycling compare to skeletal muscle?
How does max force compare?
Much slower
Maximum forces generated in greater in smooth muscle than in skeletal muscle
How is Smooth Muscle regulated compred to skeletal muscle?
Smooth - Thick Filament
Skeletal - Thin Filament
Relaxation of Smooth Muscle?
Removal of Ca2+
- SR Ca2+ ATPASE (SERCA) Pumps Ca2+ back into SR (same as skeletal)
- Ca2+ pump in plasma membrane
- Na-Ca Exchanger in Plasma Membrane
What does the removal of calcium lead to in smooth muscle?
Dephosphorylation of MLC by Myosin Light Chain Phosphatase (MLCP)
Myosin can no longer bind to actin–no cross bridge cycling
= Relaxation of muscle
What determines level of tension in smooth muscle?
Ca2+ Levels
Phasic vs Tonic Contractions
Phasic - Contracts rhythmically or intermittently; quick influx of Ca2+, cross-bridge phosphorylation, force peak, then return to baseline
Tonic - Contracts continuously; Same intracellular Ca2+, cross-bridge phosphorylation, but does not return to baseline
Tonic Contractions: Force Generation
Latch State?
Force slowly increases and sustained at high level (sphincters example)
- - -
- Cross bridge cycling rates much slower
- Force maintained w/low MLC phosphorylation
- Myosin stays attached to actin and force continues to be generated
- Ca2+ stays above baseline (calcium fluxes)
- Tension quires low [ATP]
Smooth Muscle Contraction Regulation: Unitary Muscle
Membrane potentials are unstable
Continuous, irregular contractions independent of nerve supply–leads to different type of potentials
Smooth Muscle Potential Types:
Slow Wave
Pacemaker
Pharmacomechanical
Slow Wave: Rhythmic changes, when cross threshold get contractions
Pacemaker: Regular depolarizations, regular rhythms of contractions
Pharmacomechanical: Change in tension without change in potential
(Regulation) Control Systems in Smooth Muscle:
Contraction
Increase Activity of Ca2+ Channels
Increase release of Ca2+ from SR
Inhibit MLC Phosphatase
(Regulation) Control Systems in Smooth Muscle:
Relaxation
Block Ca2+ Channels
Open K+ channels–cell hyperpolarizes, reduces Ca2+ influx through Voltage-Gated Ca2+ channels
(Regulation) Control Systems in Smooth Muscle:
cGMP Levels
Increase = Relaxation
Activation of Autonomic NS, hormones, drugs
Nitric Oxide (NO) produced by nerves and vascular endothelial cells–activates kinases; these activate MLCP and reduce intracellular Ca2+
(Regulation) Control Systems of Smooth Muscle:
cAMP Levels
Increase = Relaxation
Stimulation of B-adrenergic or adenosine receptors (pharma agonists activate these)
cAMP-dependent kinases phosphorylates MLCK
Reduces intracellular Ca2+
Autonomic Nervous System effect on smooth muscle?
Effect Depends on Muscle!
Intestinal Smooth Muscle
Para - Membrane potential = less negative, leads to more contractions
Symp - Membrane potential = more negative, leads to less contractions
Autonomic Nervous System effect on smooth muscle?
Effect Depends on Muscle!
Bronchial (Lung) Smooth Muscle
Para - Increase in contractions
Symp - Acts on B-Adrenergic Receptors to cause relaxation
Autonomic Nervous System effect on smooth muscle?
Effect Depends on Muscle!
Blood Vessel
Symp - Acts on a-Adrenergic receptors to cause constriction
Biophysical Properties of Smooth Muscle?
Length-Tension
Maximal tension generated over wide range of lengths
(big goldilocks zone vs skeletal muscle)
Cause: Smooth Muscle only partially activated, cross-bridge kinetics slower, more shortening/lengthening than skeletal muscle
Biophysical Properties of Smooth Muscle?
Force-Velocity Relationship
Contraction velocities slowerin smooth muscles, but also depends onload
Smooth muscle velocity affected by phosphorylation of MLC
Depends on Calcium–more = phosphorylation of MLC
