Аннотация
1. The mechanisms that control release of Ca$^2+$ from the sarcoplasmic
reticulum (SR) of guinea-pig ventricular cells were studied by observing
intracellular calcium concentration (Ca$^2+$i transients) and
membrane currents in voltage-clamped guinea-pig ventricular myocytes
perfused internally with Fura-2. 2. Sarcolemmal Ca$^2+$ current
was identified through the use of tetrodotoxin (TTX) and Ca$^2+$
channel antagonists (verapamil) and agonists (Bay K 8644). 3. Changes
in Ca$^2+$i attributable to release of Ca$^2+$ from the
SR were identified through the use of ryanodine, which abolishes
the ability of the SR to release Ca$^2+$. Ryanodine-sensitive
increases in Ca$^2+$i could be elicited either by depolarization
or by repolarization (from depolarizing pulses to relatively positive
membrane potentials). 4. At appropriate voltages, it is the initial
fast change in Ca$^2+$i elicited by either depolarization or
repolarization that is abolished by ryanodine, and is defined here
as ryanodine sensitive. 5. The amplitude of the ryanodine-sensitive
Ca$^2+$i transient elicited by depolarization had a bell-shaped
dependence on membrane potential with a maximum of about 500 nM at
10 mV, and with the upper minimum between 60 and 70 mV. Verapamil-sensitive
current activated over approximately the same potential range as
the Ca$^2+$i transient, with a peak amplitude at 10 mV, and
a reversal potential of 65 mV. 6. When a holding potential of -68
mV and TTX (30 microM) were used, the most negative pulse potential
at which activation of an inward current occurred was -49 mV while
changes in Ca$^2+$i occurred at -43 mV. 7. Ryanodine-sensitive
increases in Ca$^2+$i elicited by repolarization (tail transients)
were maximal for repolarization to 0 mV. Smaller changes in Ca$^2+$i
than maximal were elicited by repolarization to both more positive
and more negative potentials than 0 mV. The peak amplitude of the
verapamil-sensitive tail currents elicited by repolarization increased
continuously as the membrane was repolarized to potentials more negative
than 60 mV. 8. Increasing depolarizing pulse duration beyond 10-20
ms did not increase the amplitude of the Ca$^2+$i transient,
but prolonged it. 9. The experimental results are compared to the
predictions of two theories on the mechanism of excitation-contraction
coupling: Ca$^2+$-induced release of Ca$^2+$ (CICR), as it
has been formulated from data in skinned cardiac cells, and a charge-coupled
release mechanism (CCRM), as it has been formulated to explain
excitation-contraction coupling in skeletal muscle. 10. Some of the
results are clearly not consistent with certain features of a charge-coupled
release mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)
- ,
- 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-,
- 2475607
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