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.

[1]  Y. Okada,et al.  Volume‐sensitive chloride channels in mouse cortical neurons: characterization and role in volume regulation , 2005, The European journal of neuroscience.

[2]  Takahiro Shimizu,et al.  ClC-3-independent, PKC-dependent Activity of Volume-sensitive Cl- Channel in Mouse Ventricular Cardiomyocytes , 2004, Cellular Physiology and Biochemistry.

[3]  D. Duan,et al.  Functional effects of novel anti-ClC-3 antibodies on native volume-sensitive osmolyte and anion channels in cardiac and smooth muscle cells. , 2003, American journal of physiology. Heart and circulatory physiology.

[4]  T. Begenisich,et al.  Secretion and cell volume regulation by salivary acinar cells from mice lacking expression of the Clcn3 Cl− channel gene , 2002, The Journal of physiology.

[5]  F. Marumo,et al.  CLC‐3 deficiency leads to phenotypes similar to human neuronal ceroid lipofuscinosis , 2002, Genes to cells : devoted to molecular & cellular mechanisms.

[6]  Takahiro Shimizu,et al.  Receptor‐mediated control of regulatory volume decrease (RVD) and apoptotic volume decrease (AVD) , 2001, The Journal of physiology.

[7]  A. Draguhn,et al.  Disruption of ClC-3, a Chloride Channel Expressed on Synaptic Vesicles, Leads to a Loss of the Hippocampus , 2001, Neuron.

[8]  B. Nilius,et al.  Differential expression of volume‐regulated anion channels during cell cycle progression of human cervical cancer cells , 2000, The Journal of physiology.

[9]  D. Duan,et al.  Molecular identification of a volume-regulated chloride channel , 1997, Nature.

[10]  Y. Okada Volume expansion-sensing outward-rectifier Cl- channel: fresh start to the molecular identity and volume sensor. , 1997, The American journal of physiology.

[11]  S. Oiki,et al.  Sensitivity of volume-sensitive Cl- conductance in human epithelial cells to extracellular nucleotides. , 1996, The American journal of physiology.

[12]  B. Wolska,et al.  Method for isolation of adult mouse cardiac myocytes for studies of contraction and microfluorimetry. , 1996, The American journal of physiology.

[13]  K. Strange,et al.  Cellular and molecular physiology of volume-sensitive anion channels. , 1996, The American journal of physiology.

[14]  K. Kirk,et al.  Swelling-activated and isoprenaline-activated chloride currents in guinea pig cardiac myocytes have distinct electrophysiology and pharmacology , 1994, The Journal of general physiology.

[15]  S. Nattel,et al.  Properties of single outwardly rectifying Cl- channels in heart. , 1994, Circulation research.

[16]  H. Xu Volume-sensitive chloride currents in cardiomyocytes isolated from ClC-3 knockout mice , 2004 .

[17]  B. Nilius,et al.  Properties of volume-regulated anion channels in mammalian cells. , 1997, Progress in biophysics and molecular biology.

[18]  C. Petersen,et al.  Osmotic swelling activates intermediate-conductance Cl- channels in human intestinal epithelial cells. , 1994, The Japanese journal of physiology.