biostudies-literature00410Palygin OAmerican Heart AssociationNIDDK NIH HHSNational Institute of Diabetes and Digestive and Kidney DiseasesNHLBI NIH HHSNational Institutes of HealthUniversity of Wisconsin-Milwaukee2636-2645https://www.ebi.ac.uk/biostudies/studies/S-EPMC6338658biostudies-literatureUnknown33(2)Adaptor protein p66Shc is overexpressed in smooth muscle cells of renal resistance vessels of hypertensive salt-sensitive rats and is involved in the regulation of renal vascular tone. We applied 2-photon laser scanning fluorescence microscopy to analyze spontaneous dynamic fluctuations in intracellular calcium concentrations ([Ca²⁺]_i) in smooth muscle cells embedded in the walls of freshly isolated renal resistance arteries. The amplitude, number of events, and frequency of spontaneous [Ca²⁺]_i oscillations triggered by endogenously released endothelin-1 were recorded in smooth muscle cells of the renal arteries. Endothelin receptor A antagonist BQ123 dramatically reduced the amplitude and frequency of spontaneous Ca²⁺ events, producing marked inhibition of renal vessels spontaneous motion. Spontaneous Ca²⁺ fluctuations in smooth muscle cells of p66Shc knockout (p66ShcKO) rats had significantly higher amplitude than in control rats. The frequency of spontaneous [Ca²⁺]_i oscillations did not change in p66ShcKO rats, suggesting that p66Shc expression did not affect endothelin-1 release from resident endothelial cells. Acute application of endothelin-1 revealed significantly elevated production of the total [Ca²⁺]_i in p66ShcKO rats. Spontaneous cytosolic Ca²⁺ oscillations in smooth muscle cells of renal vessels mediate their spontaneous motion via the endothelin-1/endothelin receptor A pathway. p66Shc decreases the amplitude of individual changes in [Ca²⁺]_i, which mitigates the spontaneous motion of renal vessels.-Palygin, O., Miller, B. S., Nishijima, Y., Zhang, D. X., Staruschenko, A., Sorokin, A. Endothelin receptor A and p66Shc regulate spontaneous Ca²⁺ oscillations in smooth muscle cells controlling renal arterial spontaneous motion.FASEB journal : official publication of the Federation of American Societies for Experimental BiologyEndothelin receptor A and p66Shc regulate spontaneous Ca²⁺ oscillations in smooth muscle cells controlling renal arterial spontaneous motion.PMC6338658R01 DK098159P01 HL116264R01 HL096647R35 HL13574917SDG33660149Staruschenko APalygin ONishijima YMiller BSZhang DXSorokin A41falseEndothelin receptor A and p66Shc regulate spontaneous Ca²⁺ oscillations in smooth muscle cells controlling renal arterial spontaneous motion.Adaptor protein p66Shc is overexpressed in smooth muscle cells of renal resistance vessels of hypertensive salt-sensitive rats and is involved in the regulation of renal vascular tone. We applied 2-photon laser scanning fluorescence microscopy to analyze spontaneous dynamic fluctuations in intracellular calcium concentrations ([Ca²⁺]_i) in smooth muscle cells embedded in the walls of freshly isolated renal resistance arteries. The amplitude, number of events, and frequency of spontaneous [Ca²⁺]_i oscillations triggered by endogenously released endothelin-1 were recorded in smooth muscle cells of the renal arteries. Endothelin receptor A antagonist BQ123 dramatically reduced the amplitude and frequency of spontaneous Ca²⁺ events, producing marked inhibition of renal vessels spontaneous motion. Spontaneous Ca²⁺ fluctuations in smooth muscle cells of p66Shc knockout (p66ShcKO) rats had significantly higher amplitude than in control rats. The frequency of spontaneous [Ca²⁺]_i oscillations did not change in p66ShcKO rats, suggesting that p66Shc expression did not affect endothelin-1 release from resident endothelial cells. Acute application of endothelin-1 revealed significantly elevated production of the total [Ca²⁺]_i in p66ShcKO rats. Spontaneous cytosolic Ca²⁺ oscillations in smooth muscle cells of renal vessels mediate their spontaneous motion via the endothelin-1/endothelin receptor A pathway. p66Shc decreases the amplitude of individual changes in [Ca²⁺]_i, which mitigates the spontaneous motion of renal vessels.-Palygin, O., Miller, B. S., Nishijima, Y., Zhang, D. X., Staruschenko, A., Sorokin, A. Endothelin receptor A and p66Shc regulate spontaneous Ca²⁺ oscillations in smooth muscle cells controlling renal arterial spontaneous motion.2019-01-01T00:00:00Z2019 Feb2024-11-20T22:01:45.231Z2020-05-22T15:26:35ZS-EPMC63386583030374110.1096/fj.201800776RR10.1096/fj.201800776rr