Cell-to-cell communication via nitric oxide modulation of oscillatory Cl(-) currents in rat intact cerebral arterioles.
1. Diffusion-mediated changes in ion channel function within blood vessels have not been demonstrated directly in a patch-clamp study. Here, we examined the hypothesis that endothelium-derived diffusible bioactive substances would modify endothelin-1 (ET-1)-evoked membrane currents in smooth muscle cells situated within intact arterioles. 2. In pieces of arterioles dissected from the rat cerebral pial membrane, patch electrodes were placed on single smooth muscle cells identified under the microscope. Under perforated patch-clamp conditions, ET-1 evoked an oscillatory inward current at negative potentials in such cells in the presence of the gap junction disrupter 18alpha-glycyrrhetinic acid. ET-1 also elicited an oscillation superimposed on a membrane depolarization in current-clamp mode. 3. The oscillatory current exhibited an outwardly rectifying current-voltage relationship, a sensitivity to niflumic acid, a requirement for inositol 1,4,5-trisphosphate (IP(3))- and caffeine-sensitive Ca(2+) stores and for external Ca(2+) and a rank order of anion permeabilities characteristic of Ca(2+)-activated Cl(-) currents (I(Ca(Cl))). 4. This oscillatory response was inhibited by bradykinin (an effect distinct from the electrical propagation of hyperpolarization) and this effect was attenuated by the NO-synthase inhibitor N(omega)-nitro-L-arginine and by the NO scavenger oxyhaemoglobin but not by the cyclo-oxygenease inhibitor indomethacin. 8-Bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) and nitroprusside closely mimicked the effect of bradykinin. 5. The present patch-clamp study has revealed diffusion-mediated cell-to-cell interaction in an intact blood vessel: bradykinin appears to cause NO to move from endothelium to smooth muscle, there to inhibit an ET-1-evoked oscillatory I(Ca(Cl)) via the NO-cGMP pathway.
Yamazaki
J
J
Department of Pharmacology, Fukuoka Dental College, Sawara-ku, Fukuoka 814-0193, Japan. junyama@college.fdcnet.ac.jp
Kitamura
K
K
D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D002450:Cell Communication / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004058:Diffusion; D019332:Endothelin-1 / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009544:Niflumic Acid / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010507:Periodicity; D010841:Pia Mater / Q000098:blood supply*; D051381:Rats; D017208:Rats, Wistar
D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D010108:Oxyhemoglobins; D009599:Nitroprusside; D019335:Nitroarginine; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D009544:Niflumic Acid; D006152:Cyclic GMP; D001920:Bradykinin; D007213:Indomethacin