Biomedical Engineering Reference
In-Depth Information
Table 6.20.
Myofilament Ca
2
+
sensitivity (Source: [
464
]). CMC stretching enhances the actin-
myosin inter
action partly by transverse compression of the filament lattice.
Increased
Decreased
Stretching
Acidosis (ischemia)
Caffeine
Elevated phosphate concentration (ischemia)
Elevated Mg
2
+
concentration (ischemia)
β
Certain inotropic drugs
-Adrenergic activation
(2) into mitochondria by mitochondrial Ca
2
+
uniporters; and (3) by extrusion for a
small amount via sarcolemmal Ca
2
+
AT P a s e s a n d N a
+
-Ca
2
+
exchangers. Sodium-
calcium exchanger that functions in its forward mode as well as sarcolemmal
and sarcoplasmic reticulum Ca
2
+
ATPases restore cytosolic Ca
2
+
concentration to
resting levels and have a lusitropic effect.
Most Ca
2
+
returns to the sarcoplasmic reticulum, where Ca
2
+
is stored by bonds
with
calsequestrin
.
68
Agent ATP is not only associated with pumping of Ca
2
+
back
into SR and removing Ca
2
+
surplus, but is also required for relaxation of the actin-
myosin cross-bridges. The stronger the contraction, the greater the Ca
2
+
reuptake.
Phospholamban
(PLb) associated with SERCA inhibits this pump. Its phos-
phorylation
69
accelerates Ca
2
+
uptake by the SERCA pump; it is enhanced by
β
-adrenergic stimulation that thus has a positive lusitropic effect. Phosphorylation
by protein kinase-A of Ca
V
1 channels increases the number of functional channels
and opening duration, as well as decreases the channel activation threshold and de-
activation rate. Phosphorylation by PKA of delayed rectifier K
+
channels increases
the activity and shortens action potential duration. Protein kinase-A is stimulated by
activated Gs protein.
Catecholamines increase inotropy in particular by phosphorylating sarcolemmal
Ca
2
+
channels and increasing Ca
2
+
influx into the cytosol during the action
potential plateau (phase 2).
Cellular acidosis decreases the sensitivity of contractile elements to Ca
2
+
(Table
6.20
). Inorganic phosphate at a concentration achieved during ischemia
reduces maximum developed force and sensitivity to Ca
2
+
ions.
Whereas phospholamban abounds in ventricles,
sarcolipin
(Sln) abounds in atria,
where it regulates SERCA2a pump. Sarcolipin reduces the affinity of SERCA
for Ca
2
+
and maximal velocity of Ca
2
+
uptake rate [
637
]. In addition, sarcol-
ipin decreases Ca
2
+
transient amplitude, hence atrial contractility, and mediates
β
-adrenergic responses in atria.
68
Two calsequestrin isoforms exist, one in the skeletal muscle, the second in the myocardium [
458
].
69
Phosphorylation of phospholamban by cAMP-dependent (PKA) or calmodulin-dependent
(CamK2) protein kinases relieves the inhibition of SERCA by phospholamban.
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