Key result
KB-R7943 inhibited both outward and inward Na+/Ca2+ exchange currents with equal potency (up to 61% and 57% at 10 microM), suggesting it is not a selective inhibitor of the reverse mode.
KB-R7943 is not a selective inhibitor of the reverse mode of Na+/Ca2+ exchange in guinea pig ventricular myocytes, as it inhibits both inward and outward currents with equal potency.
KB-R7943 nonselectively inhibits NCX currents in myocytes; challenges its use as a reverse-mode probe and leaves open selective targeting strategies.
The reverse mode of Na+/Ca2+ exchange represents an important pathway in inducing Ca2+ overload during ischemia and reperfusion. The inhibitory effects of amiloride and KB-R7943 on Na+/Ca2+ exchange current (INa/Ca) were investigated in guinea pig ventricular myocytes. Whole-cell patch clamp techniques were used under bidirectional ionic conditions and 25 mM of Na+ in pipette solution. At +50 mV, amiloride 10, 30, and 100 microM inhibited the outward INa/Ca by 15, 23, and 41%, respectively; at -80 mV, it inhibited inward INa/Ca by 6, 15, and 23%, respectively. Its inhibitory effect on outward INa/Ca was greater than that on inward INa/Ca. At +50 mV, KB-R7943 1 and 10 microM inhibited the outward INa/Ca by 29 and 61%, respectively; at -80 mV, it inhibited inward INa/Ca by 22 and 57%, respectively. KB-R7943 inhibited both directions of the exchange current with an equal potency. The data suggest that KB-R7943 is not a selective inhibitor on reverse mode of Na+/Ca2+ exchange.
No takes yet. Share an insight, caveat, or question.
Lü et al. (2002) studied this question. Amiloride and KB-R7943 was evaluated on Inhibition of outward and inward Na+/Ca2+ exchange current (INa/Ca). KB-R7943 inhibited both outward and inward Na+/Ca2+ exchange currents with equal potency (up to 61% and 57% at 10 microM), suggesting it is not a selective inhibitor of the reverse mode.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: