Silver ions induce Ca release from the SR in vitro by acting on the Ca release channel and the Ca pump

Tupling, R., and H. Green. Silver ions induce Ca2 release from the SR in vitro by acting on the Ca2 release channel and the Ca2 pump. J Appl Physiol 92: 1603–1610, 2002; 10.1152/japplphysiol.00756.2001.—Silver nitrate (AgNO3) is a sulfhydryl oxidizing agent that induces a biphasic Ca2 release from isolated sarcoplasmic reticulum (SR) vesicles by presumably oxidizing critical sulfhydryl groups in the Ca2 release channel (CRC), causing the channel to open. To further examine the effects of AgNO3 on the CRC and the Ca2 -ATPase, Ca2 release was measured in muscle homogenates prepared from rat hindlimb muscle using indo 1. Cyclopiazonic acid (CPA) and ruthenium red (RR) were used to inhibit the Ca2 -ATPase and block the CRC, respectively, before inducing Ca2 release with both AgNO3 and 4-chlorom-cresol (4-CMC), a releasing agent specific for the CRC. With AgNO3 and CPA, the early rapid rate of release (phase 1) was increased (P 0.05) by 42% (314 5 vs. 446 39 mol g protein 1 min 1), whereas the slower, more prolonged rate of release (phase 2) was decreased (P 0.05) by 72% (267 39 vs. 74 7.7 mol g protein 1 min 1). RR, in combination with AgNO3, had no effect on phase 1 (P 0.05) (314 51 vs. 334 43 mol g protein 1 min 1) and decreased phase 2 (P 0.05) by 65% (245 34 vs. 105 8.2 mol g protein 1 min 1). With 4-CMC, CPA had no effect (P 0.05) on either phase 1 or 2. With addition of RR, phase 1 was reduced (P 0.05) by 59% (2,468 279 vs. 1,004 87 mol g protein 1 min 1), and RR completely blocked phase 2. Both AgNO3 and 4-CMC fully inhibited Ca2 -ATPase activity measured in homogenates. These findings indicate that AgNO3, but not 4-CMC, induces Ca2 release by acting on both the CRC and the Ca2 -ATPase.