Ca(2+)-dependent Cl(-) channels in mouse and rabbit aortic smooth muscle cells: regulation by intracellular Ca(2+) and NO.
Ca(2+)-dependent Cl(-) (Cl(-)(Ca)) channels and their regulation by intracellular Ca(2+) concentration ([Ca(2+)](i)) and nitric oxide (NO) were characterized in mouse and rabbit aortic smooth muscle cells (SMC) using patch clamp and fura 2 imaging. Single channels (1. 8 pS) and whole cell Cl(-)(Ca) currents were activated by caffeine-induced Ca(2+) release. Single Cl(-)(Ca) channels were also activated by >/=200 nM Ca(2+) in inside-out membrane patches and remained active for >5 min in </=1 microM Ca(2+) but showed rapid rundown in 2 mM Ca(2+). Authentic NO or S-nitroso-N-acetylpenicillamine (SNAP) did not affect their activation or rundown in inside-out patches. In the whole cell, SNAP (100 microM) and 8-(4-chlorophenylthio)-guanosine 3',5'-cyclic monophosphate (50 microM) did not affect Cl(-)(Ca) current, but at a higher concentration SNAP (1 mM) induced a sustained [Ca(2+)](i) rise, accompanied by a dramatic decrease in caffeine-induced Ca(2+) release and Cl(-)(Ca) current. These results indicate that 1) mouse and rabbit aortic SMC possess 1.8-pS Cl(-)(Ca) channels that are activated by Ca(2+) release from the stores, 2) both activation and rundown of single Cl(-)(Ca) channels depend on [Ca(2+)](i), and 3) NO does not affect Cl(-)(Ca) channels directly or via cGMP but can inhibit their activation indirectly by decreasing Ca(2+) release from the stores.
Hirakawa
Y
Y
Vascular Biology Unit, Whitaker Cardiovascular Institute, Boston Medical Center, Boston, Massachusetts 02118, USA.
Gericke
M
M
Cohen
R A
RA
Bolotina
V M
VM
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016477:Artifacts; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D018118:Chloride Channels / Q000378:metabolism* / Q000502:physiology; D004553:Electric Conductivity; D007425:Intracellular Membranes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D011817:Rabbits
D018118:Chloride Channels; D009569:Nitric Oxide; D002110:Caffeine; D002118:Calcium