SEA0400 is a selective inhibitor of the Na(+)/Ca(2+) exchanger having equal 
potencies to suppress both the forward and reverse mode operation of the 
Na(+)/Ca(2+) exchanger. Present experiments were designed to study the effect of 
partial blockade of Na(+)/Ca(2+) exchanger on Ca(2+) handling in isolated rat 
ventricular myocytes. Intracellular Ca(2+) transient and cell shortening were 
measured in ventricular myocytes loaded with Fura-2-AM fluorescent dye. Partial 
blockade of Na(+)/Ca(2+) exchanger was induced by superfusion of the cells with 
SEA0400 at a concentration of 0.3 microM. Amplitude of the intracellular Ca(2+) 
transient and cell shortening was significantly increased by SEA0400 in both 
field stimulated and voltage clamped myocytes, without significant elevation of 
diastolic Ca(2+) level and the decay time constant of the Ca(2+) transient. In 
patch clamped myocytes the SEA0400 induced increase in the Ca(2+) transient and 
cell shortening was accompanied by significant reduction of peak L-type Ca(2+) 
current. These effects can be explained by the autoregulative nature of cardiac 
Ca(2+) handling, as the reduced Ca(2+) efflux from the cell results in an 
increased Ca(2+) load to the sarcoplasmic reticulum leading to increased Ca(2+) 
release, which in turn may decrease the L-type Ca(2+) current by accelaration of 
Ca(2+) dependent inactivation of L-type Ca(2+) current. Our results suggest that 
complex changes in the Ca(2+) cycling can occur after selective pharmacological 
inhibition of the Na(+)/Ca(2+) exchanger.