Page 228 - Basic _ Clinical Pharmacology ( PDFDrive )

214 SECTION III Cardiovascular-Renal Drugs

Myofibril syncytium

Digoxin
–
Interstitium
Cell membrane
+ +
Na /K -ATPase NCX Ca –L Cytoplasm
v
ATP – 2+
Na + + Ca channel blockers
K +
Ca 2+ β agonists
Trigger Ca 2+

SERCA ATP
CalS
CalS
Sarcoplasmic Ca 2+ Ca 2+
Ca 2+ reticulum
CalS

CalS CalS
RyR ATP

Ca 2+ Ca 2+ Ca 2+ sensitizers
+

Z +
Actin-tropomyosin- Myosin Myosin activators
troponin

Sarcomere

FIGURE 13–1 Schematic diagram of a cardiac muscle sarcomere, with sites of action of several drugs that alter contractility. (Mitochondria,
+
+
which are critical for the generation of ATP, are omitted for simplicity.) Na /K -ATPase, the sodium pump, is the site of action of cardiac glyco-
sides. NCX is the sodium-calcium exchanger. Ca v -L is the voltage-gated, L-type calcium channel. SERCA (sarcoplasmic endoplasmic reticulum
2+
Ca -ATPase) is a calcium transporter ATPase that pumps calcium into the sarcoplasmic reticulum. CalS is calcium bound to calsequestrin, a
2+
high-capacity Ca -binding protein. RyR (ryanodine RyR2 receptor) is a calcium-activated calcium channel in the membrane of the SR that is
triggered to release stored calcium. Z is the Z-line, which delimits the sarcomere. Calcium sensitizers act at the actin-troponin-tropomyosin
complex where activator calcium brings about the contractile interaction of actin and myosin. Black arrows represent processes that initiate
contraction or support basal tone. Green arrows represent processes that promote relaxation.