Spatiotemporal characteristics of SR Ca$^2+$ uptake and release
in detubulated rat ventricular myocytes.
J. Mol. Cell. Cardiol., 39 (5):
804--812 (November 2005)DOI: 10.1016/j.yjmcc.2005.08.005
Zusammenfassung
In cardiac ventricular myocytes, sarcoplasmic reticulum (SR) Ca$^2+$
load is a key determinant of SR Ca$^2+$ release. This release
normally occurs predominantly from SR junctions at sarcolemmal invaginations
(t-tubules), ensuring synchronous SR Ca$^2+$ release throughout
the cell. However under conditions of Ca$^2+$ overload, spontaneous
SR Ca$^2+$ release and propagating Ca$^2+$ waves can occur,
which are pro-arrhythmic. We used detubulated rat ventricular myocytes
to determine the dependence of Ca$^2+$ wave propagation on SR
Ca$^2+$ load, and the role of t-tubules in SR Ca$^2+$ uptake
and spontaneous release. After SR Ca$^2+$ depletion, recovery
of Ca$^2+$ transient amplitude (and SR Ca$^2+$ load) was
slower in detubulated than control myocytes (half-maximal recovery:
9.9+/-1.4 vs. 5.5+/-0.7 beats). In detubulated myocytes the extent
and velocity of Ca$^2+$ propagation from the cell periphery increased
with each beat and depended steeply on SR Ca$^2+$ load. Isoproterenol
(ISO) accelerated recovery, increased maximal propagation velocity
and reduced the threshold SR Ca$^2+$ load for propagation. Ca$^2+$
spark frequency was uniform across control cell width and was similar
at the periphery of detubulated cells. However, internal Ca$^2+$
spark frequency in detubulated cells was 75\% lower (despite comparable
local SR Ca$^2+$ load); this transverse spark frequency profile
was similar to that in atrial myocytes. We conclude that: (1) t-tubule
Ca$^2+$ fluxes normally control SR Ca$^2+$ refilling; (2)
Ca$^2+$ wave propagation depends steeply on SR Ca$^2+$ content
(3) SR-t-tubule junctions are important in initiating SR Ca$^2+$
release and (4) ISO enhances propagation of SR Ca release, but not
the initiation of SR Ca release events (for given SR Ca$^2+$
loads).
Beschreibung
The whole bibliography file I use.