EFFECT OF KB-R7943 ON Na+-Ca2+ EXCHANGE CURRENT IN GUINEA PIG VENTRICULAR MYOCYTES / 药学学报

ABSTRACT

AIM　To study whether KB-R7943 has selective inhibitory effect on the inward and outward Na+-Ca2+ exchange current (INa-Ca) in guinea pig ventricular myocytes. METHODS　Through setting up the model of intracellular Na+-overload during myocardial ischemia and reperfusion, the current-voltage relationship of INa-Ca was recorded using whole-cell patch clamp technique under bi-directional ionic conditions. RESULTS Currents were elicited by a declining ramp pulse depolarized immediately from holding potential of -40 mV to +60 mV, then repolarized to -100 mV at a speed of 80 mV*s-1 and returned to the holding potential under bi-directional ionic conditions, while the ［Na+］ was 25 mmol*L-1 in the pipette solution. The currents increased time-dependently and voltage-dependently which reached from (2.51±0.15) pA*pF-1 to (5.94±0.13) pA*pF-1 at +50 mV and from (-1.92±0.13) pA*pF-1 to (-3.17±0.16) pA*pF-1 at -80 mV (n=12) after 3 min and there is no significant run-down of the current. KB-R7943 10-6 mol*L-1 was found to decrease the current to (4.62±0.05) pA*pF-1 by 29.4% at +50 mV and to (-2.30±0.18) pA*pF-1 by 22.1% at -80 mV (n=5) after 5 min. While 10-5 mol*L-1 KB-R7943 was shown to decrease the current to (3.13±0.03) pA*pF-1 by 61.7% at +50 mV and to (-1.62±0.03) pA*pF-1 by 56.9% at -80 mV (n=7). CONCLUSION　KB-R7943 can block INa-Ca in guinea pig ventricular myocytes. But, it did not show selective inhibition effect on inward and outward currents.