PPP - muscles Flashcards
What are the t tubules?
invaginations of the sarcolemma on myofilaments at every Z line
What is the function of t tubules?
bring the action potential deep into cells to ensure coordinated contraction
What are the terminal cisternae?
intracellular bags of membrane that store calcium - lie underneath the t tubules
What are triads and dyads?
Triads are in skeletal muscle, dyads in cardiac
- they are the SR - t tubule interface
What connects neighbouring cardiac cells?
intercalated discs
What are some features of the cardiac action potential?
Influx due to Ca2+ and Na+
long duration - 200-400ms
length decreases if heart rate goes up
What is the purpose of the long cardiac action potential?
prevents tetany
prevents agains re-entrant arrhythmias
What is the main difference between cardiac and skeletal initiation of contraction?
Ca2+ release is driven by voltage in skeletal muscle
Ca2+ release is driven by a small Ca2+ influx in cardiac muscle
What are the Ca2+ receptors on t tubules called?
DHP receptors
What type of receptors are used to release Ca2+ from the SR?
RyR receptors
What are the steps of excitation-contraction coupling in cardiac muscle?
- AP travels into cell via t tubules
- DHP receptors are activated to allow small influx of Ca2+
- Ca2+ binds RyR on SR to induce large Ca2+ release
- Ca2+ can now activate myofilaments to contract
- Ca2+ is removed by SERCA and Na/Ca exchanger
How does Ca2+ activate contraction in cardiac muscle?
it binds to troponin C
this pulls tropomyosin out of the way to allow cross-bridge formation
What is the length-tension relationship in cardiac muscle?
increased stretch in cardiac muscle causes increased force of contraction
What 2 factors contribute to the cardiac length-tension relationship?
- increased sarcomere length causes increased cross-bridge overlap
- increasing length increases sensitivity of troponin C to Ca2+
What is the force-frequency relationship in cardiac muscle?
increasing rate of contraction leads to increased force
- also get increased Ca2+ influx
What happens to the force-frequency relationship in heart failure?
get a negative effect (increased rate decreases force)
- as SERCA is down-regulated and Na/Ca exchange is up-regulated
- get reduced ca concentration
What is the maximal/optimal sarcomere length for cardiac muscle?
2.25uM
What are the main features of smooth muscle cells?
- elongated
- non-striated
- actin fillaments are anchored by dense bodies
- dense bodies are connected by intermediate filaments
- communicate through gap junctions
- higher actin:myosin ration than other muscle
In what types of smooth muscle is an action potential not always needed for contraction?
airways and sometimes vascular
What stimulates contraction in intestinal smooth muscle?
interstitial cells of cajal
What stimulates contraction in myometrium smooth muscle?
intrinsic rhythm
What can cause Ca2+ release from the SR in smooth muscle?
- IP3
- VGCC opening
- receptor gated channel opening
What are some vasoconstriction factors?
noradrenaline (main) pressure/stretch adrenaline angiotensin II local hormones
What are some vasodilating factors?
NO (released from endothelial cells
low pH
tissue metabolites
local hormones
What is the main method of vascular smooth muscle contraction?
- Via VGCC opening:
1. Noradrenaline binds alpha 1 receptors
2. activates PLC and Rho kinase
( Rho kinase causes Ca2+ sensitisation)
3. PLC cleaves PIP2 -> DAG + IP3
4. IP3 releases Ca2+ from SR
5. DAG opens RGC membrane channels to get Na+ and Ca2+ influx
6. leads to membrane depolarisation
7. VGCC becomes activated and causes large Ca2+ influx
What is an alternative method of vascular smooth muscle contraction?
stretch activates ion channels
- get Na+ influx
- membrane depolarisation
- VGCC open
How does vascular smooth muscle actively relax?
Via No or cAMP
How does NO-mediated SM relaxation occur?
- NO diffuses into cell and activates guanylate cyclase
- GTP -> cGMP
cCMP has several effects:
- causes Ca2+ desensitisation
- activates K+ channels to cause hyperpolaisation -> VGCC close
- activation of SERCA and PMCA
How does cAMP mediated SM relaxation occur?
- adrenaline binds beta 1 receptors
- activates adenylate cyclase
- ATP -> cAMP
cAMP has 2 effects:
- K+ channel opening -> depolarisation
- SERCA and PMCA activation
How do smooth muscle fibres prevent fatigue?
- lower ATP requirement due to slow cross-bridge cycles
- possibly via latch bridge formation
How does the myosin kinase complex become activated?
calmoduin binds 4Ca2+
combines with myosin light chain kinase
How is myosin regulated in smooth muscle?
activated (phosphorylated) by myosin kinase -> can form cross bridges
dephosphorylated by myosin phosphatase
How does Ca2+ sensitisation occur?
rho kinase causes inhibition of myosin phosphatase -> less myosin is inactivated
How does Ca2+ desensitisation occur?
NO -> cGMP
cGMP activates myosin phosphatase
- more myosin is inactivated by dephosphorylation
What happens to myosin regulation when Ca2+ is removed?
the calmoduin-kinase complex falls appart
- all remaining active myosin is dephosphorylated by myosin phosphatase
What is latch-bridge formation?
- theory to explain low ATP requirement of smooth muscle
- form when myosin is inactive but still bound to actin
- cycle very slowly to maintain force
What are slow waves?
spontaneous oscillations of smooth muscle which lead to depolarisation
- can be generated by pacemaker cells or SMCs themselves
What is the main cause of action potentials in smooth muscle?
VGCC opening
What is the main cause of relaxation in smooth muscle?
hyperpolarisation
What is the difference between multi-unit and unitary smooth muscle?
multi-unit = each SMC has synpatic input (allows finer control)
unitary = some SMCs are innervated and impulse spreads through gap junctions (allows coordination)
