Abstract
The importance of Na-Ca exchange as a trigger for sarcoplasmic reticulum
(SR) Ca release remains controversial. Therefore, we measured whole-cell
Ca currents (ICa), Na-Ca exchange currents (INaCa), cellular contractions,
and intracellular Ca transients in adult rabbit cardiac myocytes.
We found that changing pipette Na concentration markedly affected
the relationship between cell shortening (or Ca transients) and voltage,
but did not affect the Ca current-voltage relationship. We then inhibited
Na-Ca exchange and varied SR content (by changing the number of conditioning
pulses before each test pulse). Regardless of SR Ca content, the
relationship between contraction and voltage was bell-shaped in the
absence of Na-Ca exchange. Next, we rapidly and completely blocked
ICa by applying nifedipine to cells. Cellular shortening was variably
reduced in the presence of nifedipine. The component of shortening
blocked by nifedipine had a bell-shaped relationship with voltage,
whereas the "nifedipine-insensitive" component of contraction increased
with voltage. With the SR disabled (ryanodine and thapsigargin pretreatment),
ICa could initiate late-peaking contractions that were approximately
70\% of control amplitude. In contrast, nifedipine-insensitive contractions
could not be elicited in the presence of ryanodine and thapsigargin.
Finally, we recorded reverse Na-Ca exchange currents that were activated
by membrane depolarization. The estimated sarcolemmal Ca flux occurring
by Na-Ca exchange (during voltage clamp steps to +30 mV) was approximately
10-fold less than that occurring by ICa. Therefore, Na-Ca exchange
alone is unlikely to raise cytosolic Ca concentration enough to directly
activate the myofilaments. We conclude that reverse Na-Ca exchange
can trigger SR Ca release. Because of the sigmoidal relationship
between the open probability of the SR Ca release channel and pCa,
the effects of ICa and INaCa may not sum in a linear fashion. Rather,
the two triggers may act synergistically in the modulation of SR
release.
- 9649393
- animals,
- biophysics,
- blockers,
- calcium
- calcium,
- channel
- comparative
- contraction,
- fluid,
- gov't,
- heart
- in
- intracellular
- ion
- male,
- membrane
- myocardial
- myocardium,
- nifedipine,
- non-p.h.s.,
- non-u.s.
- p.h.s.,
- potentials,
- rabbits,
- research
- reticulum,
- sarcoplasmic
- sodium,
- study,
- support,
- transport,
- u.s.
- ventricles,
- vitro,
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