Abstract
Defective excitation-contraction coupling in heart failure is generally
associated with both a reduction in sarcoplasmic reticulum (SR) Ca$^2+$
uptake and a greater dependence on transsarcolemmal Na$^+$-Ca$^2+$
exchange (NCX) for Ca$^2+$ removal. Although a relative increase
in NCX is expected when SR function is impaired, few and contradictory
studies have addressed whether there is an absolute increase in NCX
activity. The present study examines in detail NCX density and function
in left ventricular midmyocardial myocytes isolated from normal or
tachycardic pacing-induced failing canine hearts. No change of NCX
current density was evident in myocytes from failing hearts when
intracellular Ca$^2+$ (Ca$^2+$(i)) was buffered to 200
nmol/L. However, when Ca$^2+$(i) was minimally buffered with
50 micromol/L indo-1, Ca$^2+$ extrusion via NCX during caffeine
application was doubled in failing versus normal cells. In other
voltage-clamp experiments in which SR uptake was blocked with thapsigargin,
both reverse-mode and forward-mode NCX currents and Ca$^2+$ transport
were increased >2-fold in failing cells. These results suggest that,
in addition to a relative increase in NCX function as a consequence
of defective SR Ca$^2+$ uptake, there is an absolute increase
in NCX function that depends on Ca$^2+$(i) in the failing heart.
- 11029397
- animal,
- animals,
- artificial,
- buffers,
- caffeine,
- calcium,
- cardiac
- cells,
- congestive,
- cultured,
- disease
- dogs,
- electric
- enzyme
- exchanger,
- failure,
- female,
- gov't,
- heart
- inhibitors,
- ion
- male,
- membrane
- models,
- myocardium,
- nickel,
- p.h.s.,
- pacing,
- phosphodiesterase
- potentials,
- research
- reticulum,
- sarcoplasmic
- sodium-calcium
- stimulation,
- support,
- thapsigargin,
- transport,
- u.s.
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