Evidence for a high sensitivity of large conductance Ca2+-activated K+ channels in rat aortic smooth muscle cells to ionized irradiation

Queen's University Belfast (2007) Proc Physiol Soc 7, PC4

Poster Communications: Evidence for a high sensitivity of large conductance Ca2+-activated K+ channels in rat aortic smooth muscle cells to ionized irradiation

A. I. Soloviev1, S. M. Tishkin1, I. V. Ivanova1

1. Experimental Therapeutics, Institute of Pharmacology and Toxicology, Academy of Medical Science, Kiev, Ukraine.

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It is known that γ-irradiation significantly suppresses large conductance Ca2+-activated K+ channels (BKCa) in rat coronary artery endothelial cells (Soloviev et al. 2005), and may contribute to radiation-induced endothelium-dependent vascular disorders (Soloviev et al. 2003). The goal of this study was to evaluate the influence of whole body γ-irradiation (6 Gy) on BKCa function in rat thoracic aorta smooth muscle cells using patch-clamp technique in whole-cell modification. During irradiation, Wistar rats (250 g b.w.) were restrained in a plastic box, and the radiation beam was focused on the animal’s chest. There was no change in housing, standard food or drinking water following irradiation. The animals were closely observed for unwanted effects and there were no visible signs of discomfort or illness. On the 9th and 30th days post-irradiation the thoracic aorta was taken from animals anaesthetized with ketamine/xylasine (1 ml/kg b.w.) to obtain isolated aortic smooth muscle cells. The stimulation of freshly isolated smooth muscle control cells by increasingly depolarized voltage steps showed the current-voltage relationship which demonstrated clearly expressed outward rectification with the reversal potential of -40 ± 5 mV. The current density amplitude was 52±6 pA/pF (n=10) at +70 mV. Paxillin (500 nM), selective inhibitor of BKCa channels, being added to the external solution, decreased outward potassium current density to 21 ± 6 pA/pF. Outward currents in smooth muscle cells obtained from irradiated animals on the 9th and 30th days post-irradiation demonstrated a significant decrease of K+ current density amplitudes to 35±8 pA/pF (n=7) and 20±3 pA/pF (n=8), respectively. There was no significant shift in reversal potentials under irradiation for these whole-cell currents. Paxillin decreased K+ current from 35±8 to 20±9 pA/pF in cells obtained on 9th day post-irradiation, and was without effect on irradiated cells on 30th day post-irradiation indicating the absence of conductance through BKCa channels. In conclusion, the data obtained clearly demonstrate that non-fatal whole-body γ-irradiation suppresses a large conductance Ca2+-activated K+ channels in vascular smooth muscle cells. Radiation-induced inhibition of BKCa channels could contribute to vascular hypercontractility and an increase in arterial blood pressure.



Where applicable, experiments conform with Society ethical requirements.

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