Smooth Muscle Physiology and Pharmacology Flashcards
smooth muscle fibre structure
small and spindle shaped
mononucleated
multiunit vs unitary
multiunit: tonic, slightly stronger contractions, individual operation, fine control
unitary: phasic, constantly engaged , operate together, small number of neurons operate multiple cells via gap junctions
explain the contractile machinery of smooth muscle
same proteins as skeletal muscle
actin is anchored directly to the membrane
myosin filaments between actin filaments pull the membrane
what are dense bodies
actin anchoring points
what are dense bands
sliding filament mechanism
explain cross bridge-formation in smooth muscle
intracellular calcium levels rise and bind to calmodulin
Ca2+-calmodulin complex activates myosin light chain kinase
myosin light chain is phosphorylated on the myosin head
phosphorylation of myosin head ‘cocks’ it and increases its ATPase activity
cross bridge forms
what is calmodulin
multifunctional Ca2+ binding protein present in cytoplasm of all eukaryotic cells
had no enzymatic activity but activates other peptides
explain relaxation of smooth muscle
drop of calcium concentraion and dephosphorylation by myosin light chain phosphatase
what innervates smooth muscle
autonomic NS
arterial by sympathetic noradrenaline
other by both with ACh
what two things can EC coupling in smooth muscle
pharmacological coupling
electrochemical coupling
second messengers involved in smooth muscle EC coupling and their effects
IP3 - contraction
cGMP and cAMP - relaxation
what type of channel is primarily opened in electromechanical smooth muscle EC coupling
voltage gated L-type Ca2+ channels
vasomotor tone definition
why is it necessary
all of the smooth muscle that lines the vasculature has a resting level of contraction
if fully dilated at rest we would never be able to reduce out blood pressure
explain endothelium-dependant vasodilation
in response to vasodilating substances or shear stress the endothelial cell will synthesise nitric oxide
freely diffuses into neighbouring cells
relaxation
dilation
which enzyme does NO activate in smooth muscle cells of the vasculature
what does this lead to
guanylate cyclase
cAMP production which activates protein kinase G
why does PKG activation lead to relaxation of smooth muscle
opens membrane bound potassium channels causing hyperpolarisation
what is angina
what causes it
inadequate myocardial oxygen supply
fixed vessel narrowing and endothelial dysfunction
how do organic nitrates (e.g. GTN) cause vasodilation
act on smooth muscle cells to increase NO production
what is angina treated with
no treatment
symptoms managed with organic nitrates (GTN)
what are the primary effects of organic nitrates
induce venodilation
reduce venous pressure
reduce CO (Starling’s law)
reduce O2 demand of the heart
no more angina :)
what the secondary effects of organic nitrates
dilation of coronary collaterals allowing blood to bypass the fixed vessel narrowing (plaque)
(via smooth muscle) by which 3 ways can we treat hypertension
blocking calcium channels
opening potassium channels
blocking alpha adrenoreceptors
