Electrophysiological Effects of SN-6, a Novel Na+/Ca2+ Exchange Inhibitor on Membrane Currents in Guinea Pig Ventricular Myocytes

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We examined the effect of SN-6 on the Na+/Ca2+ exchanger (NCX) current (INCX) and other membrane currents in isolated guinea pig ventricular myocytes using the whole-cell voltage clamp technique. SN-6 suppressed the bidirectional INCX in a concentration-dependent manner. The IC50 values of SN-6 were 2.3 μM and 1.9 μM for the outward and inward components of the bidirectional INCX, respectively. On the other hand, SN-6 suppressed the unidirectional outward INCX more potently than the inward INCX, with an IC50 value of 0.6 μM. SN-6 at 10 μM inhibited the unidirectional inward INCX by only 22.4 ± 3.1%. SN-6 suppressed INCX more potentially when intracellular Na+ concentration became higher. SN-6 inhibited INa, ICa, IKr, IKs, and IK1 by about 13%, 34%, 33%, 18%, and 13%, respectively. SN-6 shortened the action potential duration (APD) by about 34% and 25% at APD50 and APD90, 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 INCX more potently than the unidirectional inward INCX. Both drugs inhibit NCX in an intracellular Na+ concentration-dependent manner. However, SN-6 affected other membrane currents less potently than KB-R7943.

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