Abstract
It has been proposed that Ca$^2+$ entry through the Na$^+$-Ca$^2+$
exchanger can contribute significantly to the trigger for Ca$^2+$
release from the sarcoplasmic reticulum (SR). We have compared the
characteristics of Ca$^2+$ release triggered by reverse-mode
Na$^+$-Ca$^2+$ exchange and by L-type Ca$^2+$ current
(ICaL) during depolarizing steps in single guinea pig ventricular
myocytes (whole-cell voltage clamp, fluo 3 and fura-red as Ca$^2+$i
indicators, 36 +/- 1 degrees C, K$^+$-based pipette solution
with 20 mmol/L Na$^+$). Conditioning pulses to +60 mV ensured
comparable Ca$^2+$ loading of the SR. In the presence of ICaL,
Ca$^2+$i transients typically have an early and rapid rising
phase reflecting Ca$^2+$ release, which has a bell-shaped voltage
dependence with a peak at +10 mV. With Ca$^2+$ entry through
Na$^+$-Ca$^2+$ exchange only (20 mumol/L nisoldipine), Ca$^2+$
release flux from the SR is decreased and directly related to the
amplitude of the depolarizing step. Ca$^2+$ release is preceded
by a significant delay (81 +/- 21 ms at +20 mV, 24 +/- 4 ms at +70
mV) related to Ca$^2+$ entry through the exchanger. Triggered
release interrupts Ca$^2+$ entry, as evidenced by reversal of
the exchanger current. At potentials positive to +40 mV, Ca$^2+$
influx through Na$^+$-Ca$^2+$ exchange, calculated from the
outward exchange current, reaches magnitudes comparable to ICaL,
but Ca$^2+$ release due to reverse-mode Na$^+$-Ca$^2+$
exchange still has a significant delay. We calculated trigger efficiency
as the ratio between the maximal rate of Ca$^2+$ release and
the Ca$^2+$ influx preceding this release; efficiency of reverse-mode
Na$^+$-Ca$^2+$ exchange is approximately four times less
than that of ICaL. With both ICaL and reverse-mode Na$^+$-Ca$^2+$
exchange present, Ca$^2+$ release is triggered by ICaL, and a
contribution of reverse-mode Na$^+$-Ca$^2+$ exchange to the
trigger could not be detected at potentials below +60 mV. These characteristics
of reverse-mode Na$^+$-Ca$^2+$ exchange predict that its
role as a trigger for Ca$^2+$ release during the action potential
is likely to be negligible.
- 9400385
- animals,
- calcium
- calcium,
- channels,
- comparative
- exchanger,
- gov't,
- guinea
- l-type,
- myocardium,
- non-u.s.
- pigs,
- research
- reticulum,
- sarcoplasmic
- sodium-calcium
- study,
- support,
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