Functional and molecular consequences of ionizing irradiation on large conductance Ca2+-activated K+ channels in rat aortic smooth muscle cells.
OBJECTIVE
The goal of this study was to evaluate the influence of gamma-irradiation on Ca(2+)-activated K(+) channel (BK(Ca)) function and expression in rat thoracic aorta.


METHODS
Aortic cells or tissues were studied by the measurement of force versus [Ca(2+)](i), patch-clamp technique, and RT-PCR.


RESULTS
Stimulation of smooth muscle cells with depolarizing voltage steps showed expression of outward K(+) currents. Paxilline, an inhibitor of BK(Ca) channels, decreased outward K(+) current density. Outward currents in smooth muscle cells obtained from irradiated animals 9 and 30 days following radiation exposure demonstrated a significant decrease in K(+) current density. Paxilline decreased K(+) current in cells obtained 9 days, but was without effect 30 days after irradiation suggesting the absence of BK(Ca) channels. Aortic tissue from irradiated animals showed progressively enhanced contractile responses to phenylephrine in the post-irradiation period of 9 and 30 days. The concomitant Ca(2+) transients were significantly smaller, as compared to tissues from control animals, 9 days following irradiation but were increased above control levels 30 days following irradiation. Irradiation produced a decrease in BK(Ca) alpha- and beta(1)-subunit mRNA levels in aortic smooth muscle cells suggesting that the vasorelaxant effect of these channels may be diminished.


CONCLUSIONS
These results suggest that the enhanced contractility of vascular tissue from animals exposed to radiation may result from an increase in myofilament Ca(2+) sensitivity in the early post-irradiation period and a decrease in BK(Ca) channel expression in the late post-irradiation period.
Soloviev
Anatoly
A
Institute of Pharmacology and Toxicology, Academy of Medical Science, 14 Eugene Pottier Str., 03057, Kiev, Ukraine. tonysolpharm@ukrpost.ua
Tishkin
Sergey
S
Ivanova
Irina
I
Zelensky
Sergey
S
Dosenko
Victor
V
Kyrychenko
Sergey
S
Moreland
Robert S
RS
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D002478:Cells, Cultured; D005720:Gamma Rays / Q000009:adverse effects*; D015640:Ion Channel Gating / Q000528:radiation effects*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000528:radiation effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D018408:Patch-Clamp Techniques; D051419:Paxillin / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014916:Whole-Body Irradiation
D051036:Large-Conductance Calcium-Activated Potassium Channels; D051419:Paxillin; D012313:RNA