caa a22 4500 606236538 CHVBK 20210128101248.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s11010-014-2262-5 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2262-5 Dapagliflozin reduces the amplitude of shortening and Ca2+ transient in ventricular myocytes from streptozotocin-induced diabetic rats [Elektronische Daten] [N. Hamouda, V. Sydorenko, M. Qureshi, J. Alkaabi, M. Oz, F. Howarth] In the management of type 2 diabetes mellitus, Dapagliflozin (DAPA) is a newly introduced selective sodium-glucose co-transporter 2 inhibitor which promotes renal glucose excretion. Little is known about the effects of DAPA on the electromechanical function of the heart. This study investigated the effects of DAPA on ventricular myocyte shortening and intracellular Ca2+ transport in streptozotocin (STZ)-induced diabetic rats. Shortening, Ca2+ transients, myofilament sensitivity to Ca2+ and sarcoplasmic reticulum Ca2+, and intracellular Ca2+ current were measured in isolated rats ventricular myocytes by video edge detection, fluorescence photometry, and whole-cell patch-clamp techniques. Diabetes was characterized in STZ-treated rats by a fourfold increase in blood glucose (440±25mg/dl, n=21) compared to Controls (98±2mg/dl, n=19). DAPA reduced the amplitude of shortening in Control (76.68±2.28%, n=37) and STZ (76.58±1.89%, n=42) ventricular myocytes, and reduced the amplitude of the Ca2+ transients in Control and STZ ventricular myocytes with greater effects in STZ (71.45±5.35%, n=16) myocytes compared to Controls (92.01±2.72%, n=17). Myofilament sensitivity to Ca2+ and sarcoplasmic reticulum Ca2+ were not significantly altered by DAPA in either STZ or Control myocytes. L-type Ca2+ current was reduced in STZ myocytes compared to Controls and was further reduced by DAPA. In conclusion, alterations in the mechanism(s) of Ca2+ transport may partly underlie the negative inotropic effects of DAPA in ventricular myocytes from STZ-treated and Control rats. Springer Science+Business Media New York, 2014 Diabetes mellitus nationallicence SGLT2 inhibitors nationallicence Dapagliflozin nationallicence Ventricular myocytes nationallicence Streptozotocin-induced diabetic rats nationallicence Hamouda N. Departments of Physiology & Pharmacology, College of Medicine & Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates aut Sydorenko V. Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine aut Qureshi M. Departments of Physiology & Pharmacology, College of Medicine & Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates aut Alkaabi J. Department of Internal Medicine, College of Medicine & Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates aut Oz M. Departments of Physiology & Pharmacology, College of Medicine & Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates aut Howarth F. Departments of Physiology & Pharmacology, College of Medicine & Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 400/1-2(2015-02-01), 57-68 0300-8177 400:1-2<57 2015 400 11010 https://doi.org/10.1007/s11010-014-2262-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2262-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hamouda N. Departments of Physiology & Pharmacology, College of Medicine & Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates aut NATIONALLICENCE 700 1- Sydorenko V. Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine aut NATIONALLICENCE 700 1- Qureshi M. Departments of Physiology & Pharmacology, College of Medicine & Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates aut NATIONALLICENCE 700 1- Alkaabi J. Department of Internal Medicine, College of Medicine & Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates aut NATIONALLICENCE 700 1- Oz M. Departments of Physiology & Pharmacology, College of Medicine & Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates aut NATIONALLICENCE 700 1- Howarth F. Departments of Physiology & Pharmacology, College of Medicine & Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 400/1-2(2015-02-01), 57-68 0300-8177 400:1-2<57 2015 400 11010