Pharmacological Inhibition of Na/Ca Exchange Results in Increased Cellular Ca2 Load Attributable to the Predominance of Forward Mode Block

Block of Na/Ca exchange (NCX) has potential therapeutic applications, in particular, if a mode-selective block could be achieved, but also carries serious risks for disturbing the normal Ca balance maintained by NCX. We have examined the effects of partial inhibition of NCX by SEA-0400 (1 or 0.3 μmol/L) in left ventricular myocytes from healthy pigs or mice and from mice with heart failure (MLP). During voltage clamp ramps with [Ca]i buffering, block of reverse mode block was slightly larger than of forward mode (by 25±5%, P