In vitro activity: S0859, an N-cyanosulphonamide compound, is a novel, selective, high-affinity generic inhibitor of NBC [(Na(+)-coupled HCO(3)(-) transporters], it is potentially important for probing the transporter's functional role in heart and other tissues. S0859 reversibly inhibited NBC-mediated pH(i) recovery (K (i)=1.7 microM, full inhibition at approximately 30 microM). In HEPES-buffered superfusates, NHE-mediated pH(i) recovery was unaffected by 30 microM S0859. With CO(2)/HCO(3) (-) buffer, pH(i) recovery from intracellular alkalosis (mediated by Cl(-)/HCO(3) (-) and Cl(-)/OH(-) exchange) was also unaffected. The time course of recovery of pH(i) and contraction was slowed by S0859, confirming that NBC is a significant controller of contractility during acidosis.

Cell Assay: pH(i) recovery from intracellular acidosis was monitored using pH-epifluorescence (SNARF-fluorophore) in guinea pig, rat and rabbit isolated ventricular myocytes. Electrically evoked cell shortening (contraction) was measured optically. With CO(2)/HCO(3) (-)-buffered superfusates containing 30 muM cariporide (to inhibit NHE), pH(i) recovery is mediated by NBC.