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

It is controversial whether the CIC-3 protein, which is one of the voltage-dependent chloride channel CIC 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 CIC-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 CIC-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 CIC-3 proteins in mouse ventricular myocytes.