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Block of I(Kur) by AVE0118 enhances atrial contractility both in patients with sinus rhythm and atrial fibrillation. The positive inotropic effect is atrial-specific and due to the changes of the action potential configuration which enhances Ca2+ entry via reverse mode Na+/Ca2+ exchange.

2-aminoethoxydiphenyl borate (2-APB) has been widely used as a blocker of the IP3 receptor and TRP channels, including store-operated calcium channels. We now show in monolayers of normal rat kidney cells (NRK/49F) that 2-APB completely and reversibly blocks gap junctional intercellular communication at concentrations similar to that required for inhibition of PGF2alpha-induced increases in intracellular calcium. Gap junctional conductances between NRK cells were estimated with single-electrode patch-clamp measurements and were fully blocked by 2-APB (50 microM), when applied extracellularly but not via the patch pipette. Half maximal inhibition (IC50) of electrical coupling in NRK cells was achieved at 5.7 microM. Similar results were obtained for human embryonic kidney epithelial cells (HEK293/tsA201) with an IC50 of 10.3 microM. Using 2-APB as an electrical uncoupler of monolayer cells, we could thus measure inward rectifier potassium, L-type calcium, and calcium-dependent chloride membrane currents in confluent NRK monolayers, with properties similar to those in dissociated NRK cells in the absence of 2-APB. The electrical uncoupling action described here is a new 2-APB property that promises to provide a powerful pharmacological tool to study single-cell properties in cultured confluent monolayers and intact tissues by electrical and chemical uncoupling of the cells without the need of prior dissociation.

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