Sarcoplasmic Reticulum Ca2+ Release Uses a Cascading Network of Intra-SR and Channel Countercurrents

In muscle, Ca2+ release from the sarcoplasmic reticulum (SR) into the cytosol is mediated through the ryanodine receptors (RyRs) and sustained by countercurrents that keep the SR membrane potential near 0 mV. Likewise, Ca2+ reuptake by the sarco/endoplasmic reticulum Ca2+ ATPase pump requires countercurrent. Although evidence has suggested that TRIC K+ channels and/or RyR K+ influx provide these countercurrents, the exact sources have not yet been determined. We used an equivalent circuit compartment model of a cardiac SR, the surrounding cytosol, and the dyadic cleft to probe the sources of countercurrent during a complete cardiac cycle.

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