Developmental Changes in mRNA Encoding Cardiac Na+/H+ Exchanger (NHE-1) in Rabbit

Inhibition of the Na+/H+ exchanger attenuates the deterioration of ventricular function during pacing-induced heart failure in rabbits

“…We are confident that effective inhibition of NHE activity was achieved, since the serum BIIB722 concentration measured 24 h after oral administration of BIIB722 averaged 0.94 F 0.40 AM (n = 9) in sham rabbits and 1.01 F 0.25 AM (n = 9) in heart failure rabbits. In isolated rat cardiomyocytes, which like rabbit cardiomyocytes express mainly NHE-1 [32,33], 1 AM BIIB722 was as effective as 10 AM cariporide in inhibiting NHE activity [23], and 10 AM cariporide completely abolished the increased NHE activity in myocytes isolated from failing as compared to sham rabbit hearts [8].…”

Functional analysis of polar amino‐acid residues in membrane associated regions of the NHE1 isoform of the mammalian Na+/H+ exchanger

“…Several regions of this protein are of particular interest, for example, the membrane-associated segment that does not traverse the membrane is reminiscent of the selectivity filter of potassium channels [24]. These amino acids (387±406) are within a region that is important for amiloride binding [9]. We have noted that this segment contains several polar amino acids, including a serine at amino acids 387 and 388, and Ser390, Glu391 and Thr392.…”

“…One of these studies demonstrated that the sequence VFFLFVLLPPI(164–173), of transmembrane segment 4 of NHE1, was involved in binding amiloride analogs [7,8]. Another study showed that a segment between transmembrane regions 8 and 10 is also involved in amiloride binding [9]. However, it is now thought that the amiloride‐binding site is not directly involved in binding and transport of Na + [10] and that other regions are important in this role [9,11].…”

“…Another study showed that a segment between transmembrane regions 8 and 10 is also involved in amiloride binding [9]. However, it is now thought that the amiloride‐binding site is not directly involved in binding and transport of Na + [10] and that other regions are important in this role [9,11]. A preliminary report has suggested that amino acid Glu262 is important for activity of the protein, but there was no detailed analysis of the activity and expression of the protein; in addition, the ability of other residues to substitute at this location in the protein was not investigated [12].…”

Developmental regulation of Na+/H+exchanger expression in fetal and neonatal mice

“…Some reports have demonstrated that the amount of NHE1 message is greater in the newborn heart compared with the adult (6,23). However, there has not been a systematic evaluation of NHE1 expression in the heart and in various tissues during the early developmental process.…”