Muscle Physiology III Flashcards
inc. Ca++ n the Myosin Light
Chain Kinase
-Myosin Light Chain Kinase activated -phophoryte -CONTRACTION
Smooth muscle contraction -Myosin II:
- 2 myosin heavy chain
- 2 myosin light chains (MLC):
- Essential MLC
- Regulator MLC
Smooth muscle contraction component
Myosin light chain kinase (MLCK)
Myosin light chain phosphatase (MLCP)
Calmodulin (regulator of contraction; homologous of Troponin C)
Ca++ (activator of contraction)
Voltage-gated 1,4 dihydropyridine calcium channels
Electromechanical coupling
Ligand-gated calcium channels
Pharmacomechanical coupling
Stretch-activated calcium channels
Myogenic regulation in arterioles (microvascular resistance)
Leak calcium channels
Unregulated
Mechanical stretch promotes inward movement of Ca++
Ca++ channel bocer
-Inhibit voltage-dependent L-type calcium channels - Dec .muscle contractility
Dihydropyridine CCB
-Act on vascular smooth muscle
Amlodipine, clevidipine, nicardipine, nifedipine, nimodipine
Clinical use: Hypertension, prevention of cerebral vasospasm (nimodipine)
Non-dihydropyridine CCB
-Act on heart:
-Diltiazem, verapamil
Clinical use: atrial fibrillation
cAMP pathway
-Enhances Ca++
reuptake
-RELAXATION
Beta-2 receptors are Gs-protein coupled:
Bronchial smooth muscle relaxation (bronchodilation)
• Uterine smooth muscle relaxation during pregnancy
• Blood vessels relaxation (vasodilation) in the skeletal muscle
Albuterol, levalbuterol, salmeterol, salbutamol (inhalation)
Bronchial smooth muscle relaxation –Bronchodilation
Clinical use: Bronchial Asthma
Terbutaline
Uterine smooth muscle relaxation in pregnant women –Tocolysis
Clinical use: premature labor
milrinone
Selective PDE-3 inhibitor Phosphodiesterase 3 (PDE-3) converts cAMP into AMP in cardiac and smooth muscle -Clinical use: short-term use in acute decompensated Heart Failure
milrinone -In cardiomyocytes:
inc . cAMP - inc. Ca++ influx - inc. Inotropy and Chronotropy
milrinone -In vascular smooth muscle
inc. cAMP – Inhibition of MLCK activity – General Vasodilation
Nitric Oxide (NO) pathway
-cGMP
-Open K+ channels:
hyperpolarization
-Inhibit Ca++ entry
-MLCP
Nitrates
Increase Nitric Oxide in vascular smooth muscle
Dilate veins»_space; arteries …… Decrease PRELOAD
Nitroglycerine, isosorbide denitrate, isosorbide mononitrate
Clinical use: angina, acute coronary syndrome
Hydralazine
inc. cGMP –vascular smooth muscle relaxation
Dilate arterioles > veins …… Decrease AFTERLOAD
Clinical use: severe hypertension (acute treatment); safe during pregnancy
Nitroprusside
inc. cGMP –vascular smooth muscle relaxation
Ca++ RELEASE
- CICR
- IP3
- Contraction
mechanism o RELAXATION
- dec. Ca++
- dec. MLCK activity
mechanism o RELAXATION-Cell repolarization
Decrease influx of Ca++
mechanism o RELAXATION-Reuptake of Ca++ to the SR:
SERCA pump
mechanism o RELAXATION-Plasma Membrane Ca++ ATPase Pump
Promote Ca++ efflux
mechanism o RELAXATION-Na+/Ca++ exchange mechanism
Promote Ca++ efflux
Latch mechanism or state
ns its full force of contraction despite reduced amount of
continuing excitation and lesser energy required for comparable sustained skeletal
muscle contraction
-Low ATP utilization
• Lower Ca++ concentration requirements
Latch mechanism or state-Importance
can maintain prolonged tonic contraction in smooth muscle for
hours with little use of energy
Latch mechanism or state-Cause (hypothesis):
myosin dephosphorylation while still attached to actin during
the crossbridge cycle
Ca++ sensitization
Decrease MLCP activity – Increase MLC phosphorylation
Ca++ de-sensitization
Increase MLCP activity – Decrease MLC phosphorylation
