The Modulation of Pacing-induced Changes in Intracellular Sodium Levels by Extracellular Ca2+in Isolated Perfused Rat Hearts

This study demonstrates the inverse relationship between extracellular free calcium ([Cao]f) and intracellular sodium ([Nai]) in isolated perfused rat hearts and thus supports the role of [Nai] in the “calcium paradox”. It also shows that the extent of the increase in [Nai] (Δ[Nai]), and the extent of the decrease in left ventricular developed pressure (ΔLVDP) in isolated perfused rat hearts, induced by pacing, is modulated by [Cacf7>o]f. At low (0.24 m ) as well as normal (1.15 m ) [Cao]f, [Naiincreased with pacing, progressively and significantly (P<0.01 andP<0.05, respectively), reaching a maximum of 12.56±0.46 and 9.22±0.16 m at 500 beats/min, respectively. At high [Cao]f(2.2 m ), however, no pacing-induced increase in [Nai] was observed. Simultaneously, within the pacing range of 250–500 beats/min, the interval–force relationship was negative for all [Cao]f. With decreasing [Cao]f, a gradually increasing Δ[Nai] was induced. We hypothesise that a [Cao]f-dependent Na–Ca exchanger activity modulates Na+uptake, and thus baseline [Nai]. During incremental pacing, the increase in pacing rate induces a [Cao]f-dependent Δ[Nai], which may interact further with the sarcolemmal Na–Ca exchanger activity. As a result, both baseline [Nai] and the pacing-induced, [Cao]f-dependent Δ[Nai] modulate the net Ca2+uptake, and thus SR Ca, in a manner that results in a modulated left ventricular force development.