Direction‐independent block of bi‐directional Na + /Ca 2+ exchange current by KB‐R7943 in guinea‐pig cardiac myocytes

We investigated the inhibitory effect of KB‐R7943 on ‘bi‐directional’ Na + /Ca 2+ exchange current (i NCX ) with the reversal potential of i NCX (E NCX ) in the middle of the ramp voltage pulse employed. Bi‐directional i NCX was recorded with ‘full’ ramp pulses given every 10 s from the holding potential of −60 mV over the voltage range between 30 and −150 mV under the ionic conditions of 140 m M [Na] o , 20 m M [Na] i , 1 m M [Ca] o and 433 n M [Ca] i with calculated E NCX at −50 mV. KB‐R7943 (0.1–100 μ M ) concentration‐dependently inhibited the current, which reversed near the calculated E NCX , indicating that the blocked current was i NCX . The inhibition levels were not significantly different between outward and inward i NCX measured at 0 and −120 mV, respectively. IC 50 of KB‐R7943 was approximately 1 μ M for both directions of i NCX . Under the bi‐directional ionic conditions, only an outward or inward i NCX was induced by positive or negative ‘half’ ramp pulses, respectively, from the holding potential of −60 mV. KB‐R7943 inhibited both direction of i NCX and the concentration‐inhibition relations were superimposable to the ones obtained by ‘full’ ramp pulses. These results indicate that KB‐R7943 inhibits i NCX direction‐independently under bi‐directional conditions. This conclusion is different from that of our previous results obtained from i NCX under uni‐directional ionic conditions, where KB‐R7943 inhibited i NCX direction‐dependently. The difference could be attributed to slow dissociation of the drug from the exchanger.British Journal of Pharmacology (1999) 128 , 969–974; doi: 10.1038/sj.bjp.0702869