Sarcoplasmic Reticulum K+ (TRIC) Channel Does Not Carry Essential Countercurrent during Ca2+ Release

摘要

The charge translocation associated with sarcoplasmic reticulum (SR) Ca²⁺ 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 Ca²⁺ equilibrium potential and SR Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ reloading, and caffeine-evoked Ca²⁺ 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 Ca²⁺ 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.