Protein kinase C-dependent inhibition of BK(Ca) current in rat aorta smooth muscle cells following gamma-irradiation.
OBJECTIVE
The aim of this study was to estimate the effects of non-fatal whole-body gamma-irradiation on outward potassium plasma membrane conductivity in rat vascular smooth muscle cells (VSMC), and to identify underlying mechanisms.


METHODS
Rats were exposed to a 6 Gy dose irradiation from a cobalt(60) source. Whole-cell potassium current was measured in freshly isolated rat aorta smooth muscle cells using standard patch-clamp technique.


RESULTS
We have determined that whole-body ionising irradiation significantly inhibits whole-cell outward K(+) current in rat aortic VSMC obtained from irradiated rats 9 and 30 days after irradiation, and this inhibition appears to be increased throughout post-irradiation period. Using selective inhibitors of small conductance Ca(2+)-activated K(+) channels (SK(Ca)), apamin (1 microM), intermediate conductance Ca(2+)-activated K(+) channels (IK(Ca,)), charybdotoxin (1 microM) and a large conductance Ca(2+)-activated K(+) channels (BK(Ca)), paxilline (500 nM), we established that the main component of whole-cell outward K(+) current in rat aortic VSMC is due to BK(Ca). It is clear that on the 9th day after irradiation paxilline had only a small effect on whole-cell outward K(+) current in VSMC, and was without effect on the 30th day post-irradiation, suggesting complete suppression of the BK(Ca) current. The PKC inhibitor, chelerythrine (100 nM), effectively reversed the suppression of whole-cell outward K(+) current induced by ionising irradiation in the post-irradiation period of 9 and 30 days.


CONCLUSIONS
The results suggest that irradiation-evoked inhibition of the BK(Ca) current in aortic VSMC is mediated by PKC. Taken together, our data indicate that one of the mechanisms leading to elevation of vascular tone and related arterial hypertension development under ionising irradiation impact is a PKC-mediated inhibition of BK(Ca) channels in VSMC.
Kizub
Igor V
IV
Experimental Therapeutics Department, Institute of Pharmacology and Toxicology of Academy of Medical Sciences of Ukraine, Kiev, Ukraine. buzzmann@ukr.net
Pavlova
Oleksandra O
OO
Ivanova
Irina V
IV
Soloviev
Anatoly I
AI
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology*; D004553:Electric Conductivity; D004594:Electrophysiology; D005720:Gamma Rays; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013997:Time Factors; D014916:Whole-Body Irradiation
D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D011493:Protein Kinase C