Biomedical Engineering Reference
In-Depth Information
Cytosolic calcium concentration rises and falls very rapidly upon opening and
closing of RyR channels to ensure adequate sarcoplasmic reticulum emptying and
refilling through SERCA pumps, hence proper inotropy and lusitropy.
Calcium spark termination may be induced by junctional Ca
2
+
concentration
within the sarcoplasmic reticulum lumen that enables RyR desensitization and inac-
tivation, once a given threshold is reached [
342
]. Increased or decreased buffering
capacity of the sarcoplasmic reticulum prolongs or abbreviates the duration of Ca
2
+
release, respectively. Sensitization of RyRs with caffeine or inhibition of RyRs
with tetracaine heightens or diminishes the rate of triggering probability recovery,
respectively [
342
]. Sensitivity of RyR channels does not influence Ca
2
+
spark
amplitude recovery; the latter relies on local sarcoplasmic reticulum refilling. On
the other hand, Ca
2
+
spark triggering depends on both refilling and RyR sensitivity.
Calcium release refractoriness, which reduce the probability of channel reopen-
ing during a given time interval after closure, permit to avoid arrhythmogenesis.
Calcium release refractoriness can relies, at least partly, on the rate-limiting
conformational change of a Ca
2
+
flux controller such as calsequestrin. Recovery
of Ca
2
+
release through RyRs depends on the Ca
V
channel trigger, between-beat
changes in sarcoplasmic reticulum SR Ca
2
+
content, and
β
-adrenoceptor acitivity
that controls cardiac frequency [
342
].
5.2.3
Mitochondria
Cardiomyocytes have a richer supply of mitochondria and greater dependence on
adenosine triphosphate (ATP) than skeletal myocytes. Mitochondria cluster in the
vicinity of the nucleus and enter into contact with it to support energy requirement
for nuclear function. Mitochondria are also close to the sarcoplasmic reticulum and
sarcomere to minimize molecular transfer.
5.2.3.1
Mitochondria Populations
In the cardiomyocyte, 2 functionally and biochemically distinct populations of
mitochondria exist [
343
]: (1) subsarcolemmal mitochondria that are located be-
neath the sarcolemma and (2) interfibrillar mitochondria that are situated among
myofibrils. Activities of succinate dehydrogenase and citrate synthase are higher in
interfibrillar mitochondria with respect to subsarcolemmal mitochondria, whereas
those of carnitine palmitoyltransferase and
-glycerophosphate dehydrogenase are
nearly the same in both mitochondrium types. Interfibrillar mitochondria oxidize
tested substrates with a rate about 1.5 times faster than that of subsarcolemmal
mitochondria.
α
Search WWH ::
Custom Search