Enhanced Ca ²⁺ Current and Decreased Ca ²⁺ Efflux Restore Sarcoplasmic Reticulum Ca ²⁺ Content After Depletion

Abstract

[Ca2+]i was measured using the fluorescent indicator indo 1 in voltage-clamped ferret and rat ventricular myocytes. The Ca2+ content of the sarcoplasmic reticulum (SR) was estimated from the integral of the Na(+)-Ca2+ exchange current activated by caffeine. Refilling of the SR after caffeine removal was enhanced by stimulation. As the systolic Ca2+ transient recovered, the integral of the L-type Ca2+ current decreased and that of the Na(+)-Ca2+ exchange tail current increased. For the early pulses, the gain of Ca2+ via the Ca2+ current is greater than the loss via the exchanger, and during steady state stimulation, the fluxes are equal. The difference in the integrals gives a measure of the net gain of cell Ca2+ with each pulse. When these are summed, the calculated gain of cell Ca2+ agrees well with the increase of SR Ca2+ produced by stimulation, as measured from the caffeine-evoked currents. There was a nonlinear relationship between SR Ca2+ content and the magnitude of the systolic Ca2+ transient such that at high SR Ca2+ content a given increase of content had a greater effect on the Ca2+ transient than did an increase at low SR content. In conclusion, the effects of systolic Ca2+ on the Ca2+ current and Na(+)-Ca2+ exchange current provide a means to regulate SR Ca2+ content and thence the systolic Ca2+ transient.

Cyanide inhibits the Na+/Ca2+ exchanger in isolated cardiac pacemaker cells of the cane toad

“…Consistent with this idea, during the decay phase the relationship between [Ca 2+ ] i and current became more stable as indicated by the arrow in Fig. 4c [26]. The decay phase is almost linear as shown in Fig.…”

“…The CN À -induced reduction in I NCX could simply reflect the reduction of Ca 2+ transient during metabolic inhibition [17] and in the next section we explore whether the intrinsic properties of NCX are affected by CN À . CN À inhibited the intrinsic properties of Na + /Ca 2+ exchange To investigate whether the intrinsic properties of the NCX were changed during the metabolic inhibition, we simultaneously recorded [Ca 2+ ] i and current after rapid caffeine application [9,14,26]. This current is inhibited by 5 mM Ni 2+ and by removal of extracellular Na + , confirming that it is principally I NCX [9,14].…”

“…These results were consistent with a CN À -induced reduction of I NCX as measured by the tail currents. The intrinsic properties of NCX can be revealed by examining the relationship between caffeine-induced [Ca 2+ ] i and I NCX [26]. When I NCX is plotted against [Ca 2+ ], it displays hysteresis (Fig.…”

Termination of Ca 2+ release by a local inactivation of ryanodine receptors in cardiac myocytes

“…3B). Assuming the total releasable SR Ca 2ϩ equals the sum of Ca 2ϩ released by I Ca and caffeine, the fractional release of Ca 2ϩ induced by I Ca was 33.1 Ϯ 3.4% (n ϭ 6), consistent with previous estimations (24,40). This indicates that SR Ca 2ϩ was not depleted after the initial release, and a substantial amount of Ca 2ϩ was immediately available for release when RyRs were allowed to reopen.…”

“…This indicates that SR Ca 2ϩ was not depleted after the initial release, and a substantial amount of Ca 2ϩ was immediately available for release when RyRs were allowed to reopen. Moreover, the reduction of SR Ca 2ϩ by one-third was unlikely the primary mechanism for the refractoriness of SR because I Ca is able to trigger Ca 2ϩ release after a similar reduction of Ca 2ϩ loading (40), and Ca 2ϩ release can be elicited within 2-3 depolarizing pulses immediately after complete depletion of SR by caffeine (9,17,40), suggesting that SR is capable of releasing Ca 2ϩ with an even lower Ca 2ϩ content (less than two-thirds of normal load). Moreover, spontaneous Ca 2ϩ sparks were observed after 64% reduction in SR Ca 2ϩ loading (41).…”