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Ca
+
Tropomyosin
alpha-1 chain
Tropomyosin
beta chain
Beta-1
adrenergic
receptor
Voltage-
depenent L-type
calcium channel
Voltage-
depenent L-type
calcium channel
Voltage-
depenent L-type
calcium channel
Ryanodine
receptor 2
cAMP-dependent
protein kinase
type I-alpha
regulatory
subunit
Sodium/calcium
exchanger 1
Voltage-gated
T-type calcium
channel (ICaT)
Voltage-gated
T-type calcium
channel (ICaT)
Sarcoplasmic/endoplasmic
reticulum
calcium ATPase
2
cAMP-dependent
protein kinase
catalytic
subunit alpha
Atenolol
Ca
+
Ca
+
Ca
+
Na
+
Na
+
Ca
+
Ca
+
Ca
+
Atenolol
Atenolol
ATP
H
2
O
Ca
+
ADP
P
i
Ca
+
Ca
+
Troponin
Troponin
Muscle
Contraction
G-Protein
Signaling
Cascade
Cardiac Myocyte
Sarcoplasmic Reticulum
Low calcium is unable to
bind to troponin to displace
tropomyosin from the myosin
binding sites on the actin
filaments
Myosin and actin are unbound
allowing the filaments to
slide apart and muscle
relaxation to occur.
Actin Filament
Myosin Filament
The beta-1 adrenergic
receptor is coupled to and
activates the G-protein
signalling cascade.
Antagonizing this receptor
blocks the G-protein
signalling cascade from
occurring.
The G-protein signalling
cascade activates protein
kinase which activates
calcium channels on the
membrane, resulting in
calcium influx.
Low calcium is unable to
activate the ryanodine
receptor on the sarcoplasmic
reticulum.
Time
Membrane potential (mV)
-40mV (threshold)
Pacemaker Action Potential
Phase 0- depolarization
Phase 3- repolarization
Phase 4-spontaneous
depolarization
With atenolol
Without atenolol
Atenolol, by antagonizing
beta-1 adrenergic receptors,
decreases intracellular
Ca2+. Phase 4 spontaneous
depolarization is Ca2+
dependent, therefore
propranolol decreases the
slope of phase 4, increasing
the time it takes for
threshold to be reached and
thus slows heart rate
Cytosol
Since calcium is linked to
activation of muscle
contraction. Reducing
cytosolic calcium levels
reduces muscle contraction
Atenolol enters the
bloodstream and once it
reaches the heart, it
antagonizes the beta-1
adrenergic receptor on the
cell membrane of myocytes
such that epinephrine
stimulation of the heart is
reduced.
T-tubule
Atenolol is administered as
an oral tablet.
Mitochondria
Calcium
TPM1
TPM2
ADRB1
CACNA1C
CACNA2D2
CACNB1
RYR2
PRKAR1A
SLC8A1
CACNA1H
CACNA1G
ATP2A2
PRKACA
Atenolol
Calcium
Calcium
Calcium
Sodium
Sodium
Calcium
Calcium
Calcium
Atenolol
Atenolol
Adenosine
triphosphate
Water
Calcium
Adenosine
diphosphate
Phosphate
Calcium
Calcium
Troponin
Troponin
Muscle
Contraction
G-Protein
Signaling
Cascade