Electrophysiological Effects of SN‐6, a Novel Na + /Ca 2+ Exchange Inhibitor on Membrane Currents in Guinea Pig Ventricular Myocytes

 We examined the effect of SN‐6 on the Na + /Ca 2+ exchanger (NCX) current (I NCX ) and other membrane currents in isolated guinea pig ventricular myocytes using the whole‐cell voltage clamp technique. SN‐6 suppressed the bidirectional I NCX in a concentration‐dependent manner. The IC 50 values of SN‐6 were 2.3 μM and 1.9 μM for the outward and inward components of the bidirectional I NCX , respectively. On the other hand, SN‐6 suppressed the unidirectional outward I NCX more potently than the inward I NCX , with an IC 50 value of 0.6 μM. SN‐6 at 10 μM inhibited the unidirectional inward I NCX by only 22.4 ± 3.1%. SN‐6 suppressed I NCX more potentially when intracellular Na + concentration became higher. SN‐6 inhibited I Na , I Ca , I Kr , I Ks , and I K1 by about 13%, 34%, 33%, 18%, and 13%, respectively. SN‐6 shortened the action potential duration (APD) by about 34% and 25% at APD 50 and APD 90 , respectively. These results indicate that SN‐6 inhibits NCX in a similar manner to that of KB‐R7943. SN‐6 and KB‐R7943 inhibit the unidirectional outward I NCX more potently than the unidirectional inward I NCX . Both drugs inhibit NCX in an intracellular Na + concentration‐dependent manner. However, SN‐6 affected other membrane currents less potently than KB‐R7943.