bmsc 207 module 9

what are cardiac muscles made up of?

cardiac myocytes

what are cardiac myocytes?

• myocardial muscle cells
• are shorter, branched cells
• usually contain a single nucleus

what is cardiac muscle interconnected by?

intercalated disks

how are desmosomes linked?

mechanically

how are gap junctions linked?

electrically

what do non-contracting autorhythmic cells (pacemakers) do?

generate action potentials spontaneously

where does the depolarization start?

in the Sinoatrial node

what does long action potential duration prevent?

summation of contraction

why is Ca entry necessary for contraction in the cardiac muscle channels?

they are not mechanically coupled to ryanodine receptors

what does an increase in Ca in excitation-contraction coupling do?

triggers contraction by removing the inhibition of cross bridge cycling

what is the SERCA pump in cardiac muscle regulated by?

phospholamban

What does phospholamban inhibit in a dephosphorylated state?

SERCA

what is used for regulating force generation in skeletal muscle?

frequency summation in individual fibres and multiple-fibre recruitment

what does an increase in intracellular Ca in the cardiac myocytes enhance?

contractile force

what is the length tension relationship?

cardiac muscle generates a greater force when slightly stretched

what in the heart modifies conduction/contraction?

neuronal input

what is the heart innervated by?

the autonomic nervous system

what does the sympathetic do?

increase heart rate/conduction and contractility (autorhythmic and contractile)

what does the parasympathetic do?

decreases heart rate/conduction (autorhythmic)

what does a slightly stretched sarcomere increase?

the Ca sensitivity of the myofilaments

what does a slightly stretched sarcomere put additional tension on?

stress-activated Ca channels, increasing ca entry from extracellular space and increasing Ca induced Ca release

what can autorhythmic cells be modulated by?

sympathetic and parasympathetic neurons

at a resting heart rate of 70-72 BPM is sympathetic or parasympathetic dominant?

parasympathetic

what does parasympathetic neurons containing ACh mainly innervate the SA and AV node influencing autorhythmic myocardial cells do?

decreases the frequency of action potentials (decreasing heart rate)

what happening when ACh acts on muscarinic (M2) cholinergic receptors?

opens K+ channels and closes T-type Ca channels and HCN channels

what does increased Na+ conductance through HCN channels and Ca through T-type channels cause?

• cells reach threshold more rapidly
• a decreased level of repolarization

what kinds of cells is smooth muscle made up of?

uninucleate cells

what shape in smooth muscle?

spindle-shaped

is there troponin and T-tubules in smooth muscle?

no they are absent

what forms extensive cytoskeletal structure?

intermediate filaments (non-contractile) and dense bodies (similar to z-lines)

what are thin filaments are anchored to?

to the cell membrane or dense bodies

what are the 6 major groups that smooth muscle is divided into?

• Vascular (blood vessels walls)
• Gastrointestinal (walls of digestive tract and associated organs, ex. gallbladder)
• urinary (wall of bladder and ureters)
• respiratory (airway passages)
• reproductive (uterus in females and other reproductive structures in males and females)
• ocular (iris and ciliary body)

what does unitary (single unit) smooth muscle contain?

contains gap junctions similar to cardiac muscle cell

what does unitary (single unit) smooth muscle allow?

allows coordinated contraction of many cells causing muscle to contract as a single unit

what is the unitary (single unit) smooth muscle often referred to as?

visceral smooth muscle

is multiunit smooth muscle electrically coupled?

no

where is multiunit smooth muscle located?

iris and ciliary body of the eye, in the male reproductive tract and in the uterus except just prior to labor and delivery

what is smooth muscle usually innervated by?

the autonomic nervous system (sympathetic and parasympathetic)

what can smooth muscle be innervated by?

multiple neurons, capable of releasing different neurotransmitters

what can alter smooth muscle tension?

circulating hormones, stretch and local factors, including paracrine signals, acidity, oxygen and carbon dioxide concentration, and osmolarity

what can action potentials be initiated by?

neural, hormonal, mechanical stimulation

where do action potentials usually occur?

unitary smooth muscle

why is repolarization slower in smooth muscle?

because Ca channels inactivate slowly and there is a delayed activation of voltage gated K+ and in some cases Ca activated K+ channels

where do action potentials usually do not occur?

multiunit smooth muscle

what do autonomic neurons create?

a local depolarization that spreads electrotonically (graded fashion) throughout the muscle fibre triggering Ca entry

what is electromechanical coupling?

contraction due to electrical signaling

what three mechanisms increases both extracellular entry and intracellular release of Ca activate contraction and cytosolic?

• Ca entry through voltage gated channels or ligand gated ion channels
• Ca release from the SR
• Ca entry through voltage-independent channel

what do smooth muscle cells that respond to graded stimulation or action potentials produce?

an influx of Ca through voltage-gated L-type Ca channels

what can IP3 pathways cause?

contraction with minimal depolarization and negligible extracellular Ca influx

what does depletion of Ca in the SR cause?

activation of store-operated channels

what does the activation of store-operated channels cause?

a Ca influx across the cell membrane. allows Ca to remain elevated and replenishes SR

what do Orai-q proteins make up?

Ca channel on cell membrane

what is pharmacomechanical coupling?

when Ca is release from DR via IP3 pathway and entry of Ca via store operated channels are voltage independent

what does a stretch of smooth muscle cause?

• an internal release of Ca from the SR through the ryanodine receptor
• phosporylation of the myosin light chain leading to contraction

True or false. in smooth muscle myosin ATPase must be activated.

True

what is myosin light chain kinase (MLCK)?

the Ca - Calmodulin complex then activated an enzyme

what must the regulatory light chain be dephosphorylated by?

myosin light chain phosphatase

what is the latch state?

when even after dephosphorylation of regulatory light chain some smooth muscle can maintain force for an extended period of time with little ATP

how can neurotransmitters, hormones and paracrine molecules alter smooth muscle Ca sensitivity?

by modulating myosin light chain phosphatase (MLCP)

what does the contractile force in smooth muscle largely depend on?

the balance of MLC phosphorylation and dephosphorylation

what is MLC phosphorylation regulated by?

the Ca - CaM complex, which in turn depends on levels of intracellular Ca

which type of muscle can regulate Ca over the widest range?

smooth muscle

how do you have contractile control?

by regulating Ca sensitivity of proteins regulating contraction

what makes you have greater contraction at lower Ca?

inhibiting MLCP or activating MLCK

where are skeletal muscles located?

mostly attached to skeleton but also to other muscles

where are smooth muscles located?

walls of hollow organs, blood vessels

where are cardiac muscles located?

the heart

what is the main function for skeletal muscle?

movement, posture, heat production

what is the main function for smooth muscle?

varies with structure involved

what is the main function for cardiac muscle?

pumps blood out of heart

where is the initiation of contraction in the skeletal muscle?

exclusively neural (neuromuscular transmission)

where is the initiation of contraction in smooth muscle?

myogenic (pacemaker), neural, stretch, hormonal, local mediators

Where is the initiation of contraction in cardiac muscle?

myogenic (pacemaker)

What is the role of innervation in skeletal muscle?

initiate contraction

what is the role of innervation in smooth muscle?

can initiate/modify contraction

what is the role of innervation in cardiac muscle?

modify conduction/contraction

what is the innervation and level of control in skeletal muscle?

somatic nerves, conscious/subconscious regulation

what is the innervation and level of control in smooth muscle?

autonomic nerves/involuntary

what is the innervation and level of control in cardiac muscle?

autonomic nerves/involuntary

are muscle cells electrically coupled (gap junctions) in skeletal muscles?

no

are muscle cells electrically coupled (gap junctions) in smooth muscle?

varies (unitary versus multiunit)

are muscle cells electrically coupled (gap junctions) in cardiac muscle?

yes (within each chamber)

is the mechanism of contraction the same for all muscle (skeletal, smooth and cardiac)?

yes they all have sliding filament mechanism?

is there the presence of thick (myosin) and thin (actin) filaments in each type of muscle?

yes

is there the presence of troponin and tropomyosin in skeletal muscle?

yes

is there the presence of troponin and tropomyosin in smooth muscle?

tropomyosin only

is there the presence of troponin and tropomyosin in cardiac muscle?

yes

which of the three muscles have T-tubules present?

skeletal and cardiac

Is crossbridges cycling turned on by calcium in all three muscle types?

yes, expect for skeletal and cardiac muscle it has a thin filament control and for smooth muscle it has a thick filament control

what is the source of cytosolic calcium in skeletal muscle?

sarcoplasmic reticulum (SR)

what is the source of cytosolic calcium in smooth muscle?

extracellular fluid + SR (varies)

what is the source of cytoplasmic calcium in cardiac muscle?

extracellular fluid (10%) + SR (90%)

what is the nature of calcium sensor for contraction in skeletal muscle?

troponin

what is the nature of calcium sensor for contraction in the smooth muscle?

calmodulin

what is the nature of calcium sensor for contraction in the cardiac muscle?

troponin

what causes the activation of cross-bridge cycling in skeletal muscle?

Ca binding to troponin/removal of interaction block between myosin and actin

What causes the activation of cross-bridge cycling in smooth muscle?

binding to calmodulin/activation of myosin light chain kinase and phosphorylation of myosin light chain

what causes the activation of cross-bridge cycling in cardiac muscle?

Ca binding to troponin/removal of interaction block between myosin and actin

what happens at the termination of contraction of skeletal muscle?

breakdown of acetylcholine/re-uptake of Ca in SR

what happens at the termination of contraction of smooth muscle?

decrease sarcoplasmic Ca/myosin light chain phosphatase