Ionizing non-fatal whole-body irradiation inhibits Ca2+-dependent K+ channels in endothelial cells of rat coronary artery: possible contribution to depression of endothelium-dependent vascular relaxation.
OBJECTIVE
The goal of this study was to evaluate the influence of ionizing irradiation on large conductance Ca2+-dependent potassium (BKCa) channels in rat coronary endothelial cells.


METHODS
Rats were exposed to a 6 Gy dose from a cobalt60 source. Experimental design of this study comprised recording of contractile force using isolated rat aortic rings and whole-cell patch clamp techniques to study whole-cell potassium currents in isolated rat coronary artery endothelial cells.


RESULTS
It has been shown that outward potassium currents in endothelial cells 9 days after irradiation appear to be suppressed or even totally abolished. The reversal potential for these currents in irradiated cells was shifted to more positive values. Paxilline (500 nM), an inhibitor of BKCa channels, had no or only a negligible effect on irradiated cells. The experiments using isolated aortic rings demonstrated that both paxilline and irradiation significantly shifted the acetylcholine dependent concentration-relaxation response curve to the right. Irradiated tissues were insensitive to paxilline.


CONCLUSIONS
The results suggest that non-fatal, whole-body gamma-irradiation suppresses large conductance, calcium-activated potassium channels, which control the driving force for Ca2+ entry and therefore Ca2+ dependent nitric oxide (NO) synthesis in endothelial cells. This may contribute, in part, to radiation-induced endothelium dysfunction and an increase in arterial blood pressure.
Tishkin
Sergey M
SM
Institute of Pharmacology and Toxicology, Academy of Medical Sciences, Kiev, Ukraine.
Rekalov
Vladimir V
VV
Ivanova
Irina V
IV
MoreLand
Robert S
RS
Soloviev
Anatoly I
AI
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D005720:Gamma Rays; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D018408:Patch-Clamp Techniques; D051419:Paxillin / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000528:radiation effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014916:Whole-Body Irradiation
D051419:Paxillin; D024681:Potassium Channels, Calcium-Activated; D014665:Vasodilator Agents; D000109:Acetylcholine