Pharmacological Inhibition of Na/Ca Exchange Results in Increased Cellular Ca@@u2+@ 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@@u2+@ balance maintained by NCX. We have examined the effects of partial inhibition of NCX by SEA-0400 (1 or 0.3 ^kmol/L) in left ventricular myocytes from healthy pigs or mice and from mice with heart failure (MLP@@u-/-@). During voltage clamp ramps with [Ca@@u2+@]@@di@ buffering, block of reverse mode block was slightly larger than of forward mode (by 25^c5%, P