Exposure to radiation elicits arterial hypertension and endothelial dysfunction in mammals (Soloviev et al. 2002, 2003). The BKCa channel is one of the established radiation targets (Soloviev et al. 2005). The goal of this study was to clarify whether KCNMA1 gene silencing mimics the vascular effects of ionized irradiation in experimental animals since it is known that small interference RNA (siRNA) can be used to dissect the function of different splice variants of ion channel encoding genes. The siRNA to KCNMA1 gene (Metabion, Germany) was injected into the rats intravenously at a dose of 800 µmol/kg in accordance with standard Metabion protocol for siRNA annealing. On the 7th day after siRNA administration the thoracic aorta was taken from animals anesthetized with ketamine (37.5 mg/kg b.w., IP) and xylazine (5 ml/kg b.w. IP) to obtain isolated smooth muscle cells (SMC) and smooth muscle (SM) rings for patch-clamp technique, contractile recordings and real time PCR analysis (protein expression was confirmed by Western blot method). Whole-body irradiation (total dose 6 Gy) was performed with gamma rays delivered at a rate of 0.8 Gy/min from a cobalt source. Outward potassium currents stimulated by a depolarized voltage step to +70 mV were 30±1, 11±1, and 13±1 pA/pF in control, irradiated (6 Gy) and KCNMA1 gene knockdown SMC, respectively (n=12, P<0.05). Paxilline (500 nM)-sensitive components were 25±2, 5±1, 9±1 pA/pF, respectively (n=12, P<0.05). The expression profile of BKCa mRNA transcripts in SM appeared to be significantly decreased in silencing SM similar to irradiated SM when the level of BKCa expression had decreased. The silencing of KCNMA1 gene led to a significant increase in arterial blood pressure in 30% of animals only, while radiation produced hypertension development in 90% of all observations. Standard acetylcholine test showed no abnormalities in endothelium-dependent relaxant responses in SM obtained from rats with silencing KCNMA1 gene in contrast to irradiated animals. At the same time KCMA1 gene silencing SM demonstrated an increased sensitivity to arterenol – mean values of pD2 (-log EC50) are 6.1±0.1 control, and 7.6±0.2 (n=10, P< 0.01) KCMA1 gene silencing SM. Therefore, radiation alters the form and function of the BKCa channel and this type of ionic channel may contribute to related vascular abnormalities. Nevertheless, it is unlikely that BKCa can operate as a crucial factor for radiation-induced arterial hypertension. It is clear that the underlying mechanism producing the alterations of vascular function under irradiation is multifaceted.