Smooth Muscle Flashcards
1
Q
Smooth Muscle
A
- more variable than skeletal
- must operate over a range of lengths
- layers run in several direction - contract and relax much more slowly
- use less energy to generate and maintain force
- can sustain contraction without fatigue
- contraction initiated electrically or chemically
- controlled by autonomic nervous system
- Ca2+ from Extracellular space and/or SR
- Ca2+ initiates cascade eventually turning on myosin ATPase
2
Q
Properties of Smooth Muscle
A
- spindle-shaped, uninucleate cells
- NO troponin and T-tubules
- intermediate filaments (non-contractile) and dense bodies (similar to z-lines) form extensive cytoskeletal structure
- thin filaments are anchored to the cell membrane or dense bodies
3
Q
Smooth Muscle Caterogies
A
- Location
- Contraction Pattern
- Communication with neighbouring cells
- unitary and multiunit
4
Q
Location of Smooth Muscle
A
- Vascular: blood vessel walls
- Gastrointestinal: walls of digestive tract and associated organs
- Urinary: wall of bladder and ureters
- Respiratory: airway passages
- Reproductive: uterus in females and other structures
- Ocular: iris and ciliary body
5
Q
Contraction Pattern
A
- Phasic smooth muscle that is usually relaxed (esophagus)
- Phasic smooth muscle that cycles between contraction and relaxation (intestine)
- Tonic smooth muscle usually contracted (sphincter)
- Tonic smooth muscle who contraction is varied as needed (vascular smooth muscle)
6
Q
Unitary Smooth Muscle
A
- single unit
- contains gap junction similar to cardiac muscle cell
- allows coordination of many cells causing muscle to contract as a single unit
- referred to as Visceral Smooth Muscle
7
Q
Multiunit Smooth Muscle
A
- not electrically coupled
- behave on their own, not as a unified unit
- iris and ciliary body of eye, in the male reproductive tract and in uterus except prior to delivery
8
Q
Smooth Muscle Contract Because…
A
- response to synaptic transmission or electrical coupling
- innervated by the autonomic nervous system
- can be innervated by multiple neurons, capable of releasing different neurotransmitters
9
Q
Different Receptor Subtypes in Smooth Muscle
A
- alpha-adrenergic: Gi vessel constriction
2. beta-adrenergic: airway dilation
10
Q
Alterations of Smooth Muscle Tension
A
- circulating hormones, stretch and local factors
- paracrine signals, acidity, oxygen and carbon dioxide concentration, and osmolarity
11
Q
Action Potentials of Smooth Muscles
A
- can be initiated by neural, hormonal, or mechanical stimulation
- upstroke slower because Ca2+ channels propagate the AP instead of Na+
- repolarization slower because Ca2+ channels inactivate slowly and there is a delayed activation of voltage gated k+ and in some cases Ca2+-activated K+ channels
- happen only in unitary muscle
12
Q
Slow Wave Potentials in Smooth Muscle
A
- fire action potentials when they reach threshold
- slowly increase to threshold
13
Q
Pacemaker Potential
A
- always depolarize to threshold
14
Q
Contraction without Action Potentials
A
- smooth muscle cells produce a wide range of membrane potentials and in some smooth muscle Vm oscillations can lead to tonic contractions in the absence of APs
- APs don’t usually occur in multiunit smooth muscle
- autonomic neurons create a local depolarization that spreads electrontonically (graded fashion) throughout muscle fibre triggering Ca2+ entry
15
Q
Electrical Activity in Single Unit Smooth Muscle
A
- Autonomic AP initiation
- spikes and plateaus
- Spontaneous AP
- slow wave
- pacemaker
16
Q
Electrical Activity in Multiunit Smooth Muscle
A
- graded potentials
- contraction due to electrical signalling known as electromechanical coupling
17
Q
Ca2+ Activated Contraction
A
- release increased by 3 ways:
1. Ca2+ entry through voltage gated channels or ligand gated ion channels
2. Ca2+ release from SR- Ca2+ induced Ca2+ release from RyR
- IP3 Ca2+ release from IP3R
3. Ca2+ entry through voltage-indepentdent channels - store operated Ca2+ channels
- stretch activated channels
18
Q
Ca2+ Entry through Voltage-Gated Channels
A
- smooth muscle cells respond to graded stimulation or action potentials
- both produce an influx of Ca2+ through voltage-gated L-type Ca2+ channels
19
Q
Ca2+ Release from SR
A
- less SR than in skeletal and cardiac muscle
- occurs via Ca2+-induced Ca2+ release and IP3 pathway
- IP3 pathway can because contraction with minimal depolarization and negligible extracellular Ca2+ influx
20
Q
GPCR-phospholipase C Signal Transduction (alpha-adrenergic receptor)
A
- signal molecule activates receptor and associated G protein
- G protein activates phospholipase C (PLC) , an amplifier enzyme
- PLC converts membrane phospholipids into diacylglycerol (DAG), which remains in the membrane, and IP3, which diffuses into the cytoplasm
- DAG activates protein kinase C (PKC), which phosphorylates proteins
- IP3 causes release of Ca2+ from organelles, creating a Ca2+ signal
21
Q
Ca2+ Entry through Voltage-Independent Channels
A
- depletion of Ca2+ in SR causes activation of store-operated channels
- causes a Ca2+ influx across the cell membrane
- [Ca2+]i allowed to remain elevated and replenish SR
- STIM1 on SR
- Orai-1 proteins make up CA2+ channel on cell membrane
22
Q
Pharmacomechanical Coupling
A
- Ca2+ release from SR via IP3 pathway (IP3 binds to IP3 receptor)
- entry of Ca2+ via store operated channels are voltage independent and
- ex) drugs, excitatory neurotransmitters and hormones can induce smooth muscle contraction with no AP generation
- occurs when chemical signals change muscle tension through signal transduction pathways with little or no change in Vm
23
Q
Stretched Activated Contraction
A
- stretched activated ion channels in the cell membrane that lead to depolarization when activated
- Ca2+, Cl-, TRPV4, TRPC1, TRPC6
- cause an internal of Ca2+ from SR through RyR
- shown to cause phosphorylation of myosin light chain leading to contraction
24
Q
Calmodulin
A
- Ca2+ binding protein (like troponin)
- Ca2+ signal in smooth muscle
- 4 Ca2+ ions bind to calmodulin
25
Q
Initiating Cross Bridge Cycle in Smooth Muscle
A
- Ca2+ calmodulin complex activates enzyme MLCK
- MLCK phosphorylates the regulatory light chain near myosin head altering conformation and increase ATPase activity and allows it to interact with actin
- activates the thick filaments (caldesmon and calponin)
26
Q
Increasing Force Generated
A
increase Ca2+ entry > increased MLCK activated > more myosin heads activated > increased force generated
27
Q
Initiation of Cross Bridge Cycle in Smooth Muscle
A
- intracellular CA2+ concentration increase when Ca2+ enters cells and released by SR
- Ca2+ binds to calmodulin (CaM)
- Ca2+-calmodulin activates MLCK
- MLCK phosphorylates light chains in myosin heads and increases myosin ATPase activity
- active myosin crossbridges slide along actin and create muscle tension
28
Q
Cross Bridge Cycle in Smooth Muscle
A
- occurs slower
29
Q
Relaxation of Smooth Muscle
A
- Ca2+ moves back to SR and extracellular space
- Ca2+ removal does not immediately lead to relaxation
- regulatory light chain must be dephosphorylated by MLCP
- even after dephosphorylation some smooth muscle can maintain force for an extended period of time with little AP (Latch state)
30
Q
Ca2+ Sensitivity
A
- neurotransmitters, hormones and paracrine molecules alter Ca2+ sensitivity by modulating MLCP
- changes in phosphatase activity alter myosin’s response to Ca2+
31
Q
Increasing Contractile Force
A
- largely depends on the balance of MLC phosphorylation and dephosphorylation
- MLC phosphorylation is regulated by the Ca2+-CaM complex, which in turn depends on levels of intracellular Ca2+
- Contractile control by regulating Ca2+ sensitivity of proteins regulating contraction
- Inhibiting MLCP or activating MLCK leading to greater contraction at lower [Ca2+]i
