Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, Illinois, USA.
Biophys J. 2013 Sep 3;105(5):1151-60. doi: 10.1016/j.bpj.2013.07.042.
The charge translocation associated with sarcoplasmic reticulum (SR) Ca(2+) efflux is compensated for by a simultaneous SR K(+) influx. This influx is essential because, with no countercurrent, the SR membrane potential (Vm) would quickly (<1 ms) reach the Ca(2+) equilibrium potential and SR Ca(2+) release would cease. The SR K(+) trimeric intracellular cation (TRIC) channel has been proposed to carry the essential countercurrent. However, the ryanodine receptor (RyR) itself also carries a substantial K(+) countercurrent during release. To better define the physiological role of the SR K(+) channel, we compared SR Ca(2+) transport in saponin-permeabilized cardiomyocytes before and after limiting SR K(+) channel function. Specifically, we reduced SR K(+) channel conduction 35 and 88% by replacing cytosolic K(+) for Na(+) or Cs(+) (respectively), changes that have little effect on RyR function. Calcium sparks, SR Ca(2+) reloading, and caffeine-evoked Ca(2+) release amplitude (and rate) were unaffected by these ionic changes. Our results show that countercurrent carried by SR K(+) (TRIC) channels is not required to support SR Ca(2+) release (or uptake). Because K(+) enters the SR through RyRs during release, the SR K(+) (TRIC) channel most likely is needed to restore trans-SR K(+) balance after RyRs close, assuring SR Vm stays near 0 mV.
与肌浆网 (SR) Ca(2+) 外排相关的电荷转移通过同时的 SR K(+) 内流得到补偿。这种内流是必不可少的，因为没有逆流，SR 膜电位 (Vm) 将很快（<1ms）达到 Ca(2+) 平衡电位，SR Ca(2+) 释放将停止。已经提出，SR K(+) 三聚体细胞内阳离子 (TRIC) 通道携带必需的逆流。然而，ryanodine 受体 (RyR) 本身在释放过程中也携带大量的 K(+) 逆流。为了更好地定义 SR K(+) 通道的生理作用，我们在皂素通透的心肌细胞中比较了 SR Ca(2+) 转运在限制 SR K(+) 通道功能前后的情况。具体来说，我们通过用 Na(+) 或 Cs(+) （分别）取代细胞溶质 K(+) 来减少 35%和 88%的 SR K(+) 通道传导，这些变化对 RyR 功能几乎没有影响。钙火花、SR Ca(2+) 再填充和咖啡因诱发的 Ca(2+) 释放幅度（和速率）不受这些离子变化的影响。我们的结果表明，SR K(+)（TRIC）通道携带的逆流对于支持 SR Ca(2+) 释放（或摄取）不是必需的。因为在释放过程中 K(+) 通过 RyRs 进入 SR，所以 SR K(+)（TRIC）通道很可能在 RyRs 关闭后用于恢复跨 SR K(+) 平衡，确保 SR Vm 保持在 0mV 附近。
