Smooth Muscle Physiology and Pharmacology

Question 1

smooth muscle fibre structure

Answer 1

small and spindle shaped
mononucleated

Question 2

multiunit vs unitary

Answer 2

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

Question 3

explain the contractile machinery of smooth muscle

Answer 3

same proteins as skeletal muscle
actin is anchored directly to the membrane
myosin filaments between actin filaments pull the membrane

Question 4

what are dense bodies

Answer 4

actin anchoring points

Question 5

what are dense bands

Answer 5

sliding filament mechanism

Question 6

explain cross bridge-formation in smooth muscle

Answer 6

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

Question 7

what is calmodulin

Answer 7

multifunctional Ca2+ binding protein present in cytoplasm of all eukaryotic cells
had no enzymatic activity but activates other peptides

Question 8

explain relaxation of smooth muscle

Answer 8

drop of calcium concentraion and dephosphorylation by myosin light chain phosphatase

Question 9

what innervates smooth muscle

Answer 9

autonomic NS
arterial by sympathetic noradrenaline
other by both with ACh

Question 10

what two things can EC coupling in smooth muscle

Answer 10

pharmacological coupling
electrochemical coupling

Question 11

second messengers involved in smooth muscle EC coupling and their effects

Answer 11

IP3 - contraction
cGMP and cAMP - relaxation

Question 12

what type of channel is primarily opened in electromechanical smooth muscle EC coupling

Answer 12

voltage gated L-type Ca2+ channels

Question 13

vasomotor tone definition
why is it necessary

Answer 13

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

Question 14

explain endothelium-dependant vasodilation

Answer 14

in response to vasodilating substances or shear stress the endothelial cell will synthesise nitric oxide
freely diffuses into neighbouring cells
relaxation
dilation

Question 15

which enzyme does NO activate in smooth muscle cells of the vasculature
what does this lead to

Answer 15

guanylate cyclase
cAMP production which activates protein kinase G

Question 16

why does PKG activation lead to relaxation of smooth muscle

Answer 16

opens membrane bound potassium channels causing hyperpolarisation

Question 17

what is angina
what causes it

Answer 17

inadequate myocardial oxygen supply
fixed vessel narrowing and endothelial dysfunction

Question 18

how do organic nitrates (e.g. GTN) cause vasodilation

Answer 18

act on smooth muscle cells to increase NO production

Question 19

what is angina treated with

Answer 19

no treatment
symptoms managed with organic nitrates (GTN)

Question 20

what are the primary effects of organic nitrates

Answer 20

induce venodilation
reduce venous pressure
reduce CO (Starling’s law)
reduce O2 demand of the heart
no more angina :)

Question 21

what the secondary effects of organic nitrates

Answer 21

dilation of coronary collaterals allowing blood to bypass the fixed vessel narrowing (plaque)

Question 22

(via smooth muscle) by which 3 ways can we treat hypertension

Answer 22

blocking calcium channels
opening potassium channels
blocking alpha adrenoreceptors