ClC-3-independent, PKC-dependent activity of volume-sensitive Cl channel in mouse ventricular cardiomyocytes.
Volume-sensitive outwardly rectifying (VSOR) Cl- channels are activated during osmotic swelling and involved in the subsequent volume regulation in most animal cells. To test the hypothesis that the ClC-3 protein is the molecular entity corresponding to the VSOR Cl- channel in cardiomyocytes, the properties of VSOR Cl- currents in single ventricular myocytes isolated from ClC-3-deficient (Clcn3(-/-)) mice were compared with those of the same currents in ClC-3-expressing wild-type (Clcn3(+/+)) and heterozygous (Clcn3(+/-)) mice. Basal whole-cell currents recorded under isotonic conditions in ClC-3-deficient and -expressing cells were indistinguishable. The biophysical and pharmacological properties of whole-cell VSOR Cl- currents in ClC-3-deficient cells were identical in ClC-3-expressing cells. The VSOR Cl- current density, which is an indicator of the plasmalemmal expression of functional channels, was essentially the same in cells isolated from these 3 types of mice and C57BL/6 mice. Activation of protein kinase C (PKC) by a phorbol ester was found to upregulate VSOR Cl- currents in ClC-3-deficient and -expressing cardiomyocytes. This effect is opposite to the reported downregulatory effect of PKC activators on ClC-3-associated Cl- currents. We thus conclude that functional expression of VSOR Cl- channels in the plasma membrane of mouse cardiomyocytes is independent of the molecular expression of ClC-3.
Gong
Weiqin
W
Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
Xu
Hongtao
H
Shimizu
Takahiro
T
Morishima
Shigeru
S
Tanabe
Shigeru
S
Tachibe
Takanori
T
Uchida
Shinichi
S
Sasaki
Sei
S
Okada
Yasunobu
Y
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D004553:Electric Conductivity; D015870:Gene Expression; D006352:Heart Ventricles / Q000166:cytology; D007552:Isotonic Solutions / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology
D018118:Chloride Channels; C115376:ClC-3 channel; D007552:Isotonic Solutions; D012333:RNA, Messenger; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid