Single-channel properties of volume-sensitive Cl^- channel in ClC-3-deficient cardiomyocytes

It is controversial whether the ClC-3 protein, which is one of the voltage-dependent chloride channel ClC family members, is a candidate for the volume-sensitive outwardly rectifying (VSOR) Cl^- channel per se or its regulator. Here, for the first time, we examined the single-channel properties of the VSOR Cl^- channel in ventricular myocytes isolated from ClC-3 - deficient mice. The single-channel current induced by cell swelling exhibited Cl^- selectivity, mild outward rectification, and an intermediate unitary conductance (around 38 pS). A Cl^- channel blocker, 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS), reversibly inhibited the outward current. These single-channel properties were identical with those in ClC-3 expressing wild-type ventricular myocytes. These results indicate that the single-channel activity of the VSOR Cl^- channel is independent of the expression of ClC-3 proteins in mouse ventricular myocytes.